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Feb. 17, 1998
No. 15 Virgina Travels to Wake Forest
#15 Virginia (17-7, 8-6) at Wake Forest (4-12, 0-15)
Feb. 18, 1998 7:00 p.m.
WINA Radio 1070 AM No TV
Lawrence Joel Coliseum (14,407) Winston-Sale m, N.C.
Quick Notes on Virginia
Series With Wake Forest
This is the 42nd meeting between the two teams. Virginia holds a 40-1 record in the series and has won 38 straight against the Demon Deacons. The Cavaliers have never lost to Wake Forest in Winston-Salem.
Last Game Vs. Wake Forest (Jan. 18, 1998)
Lisa Hosac scored 12 of her 16 points in the first half as No. 15 Virginia jumped in front early and coasted to a 65-55 victory over Wake Forest on Jan. 18. DeMya Walker led the Cavaliers with 23 points. Mimi McKinney scored 10 points, and she and Hosac each contributed seven rebounds.
Virginia went ahead 11-4 in the first three minutes of the game with baskets by all five starters and stretched the advantage to 17 by halftime. Wake Forest was led by Heidi Coleman with 16 points, and Olivia Dardy added 10.
Wake Forest out-rebounded Virginia 43-30, but shot just 37.7
percent from the field (220-53). The Cavaliers shot 48.3 percent from the
field (29-60).
How the Teams Match Up Tonight
Virginia Wake Forest
Points 70.3 57.3
Points Allowed 64.9 67.2
Rebounds 39.9 36.3
Rebound Margin -1.1 -1.9
FG% defense .388 .423
3-pt FG % .297 .309
Assists 13.8 11.7
Turnovers 20.4 21.7
Blocks 5.8 1.7
Steals 11.8 6.8
Head Coach Debbie Ryan
Head Coach Debbie Ryan, in her 21st season, brings a career record of 479-162 (.747) into tonight's game. Ryan is the ACC leader in conference wins (199) and winning percentage. She needs just one more win to notch her 200th conference win.
Guarded Condition
Head Coach Debbie Ryan is a strong candidate for ACC Coach of the Year after beginning the season with two starting guards falling to season-ending injuries and all but two of the remaining guards suffering injuries that have kept them out of the line-up at one time or another this season.
Senior Monick Foote made the decision to redshirt this season due to a chronic ankle problem (right) and a stress fracture in the same leg that developed during the summer. Foote wanted to take the time to properly rehab the leg and comeback for a healthy senior year in 1998-99.
Junior Tiffany Bower suffered a torn left achilles tendon on the third day of practice and will not play this season. Bower worked extremely hard over the summer to come back from a torn right achilles tendon which she suffered on the eve of the NCAA Tournament last March and was cleared to play this season.
Sophomore Renee Robinson suffered a concussion in the Old Dominion (1-27-98) game that kept her sidelined for two games and junior Kate Mooney suffered a one-inch gash on her head during the N.C. State (2-12-98) game that kept her out of most of the first half.
In addition, senior Mimi McKinney has played the entire season on a very sore left knee which was recently diagnosed as a tear in the ligament. She did not play in the Dec. 8 game vs. Mt. St. Mary's because of a bone bruise on her left knee.
Freshman guards Erin Stovall and Katie Tracy have remained healthy this season.
Walker Becomes 15th Player To Reach 1000
DeMya Walker became the 15th player in school history to score 1000 career points when she connected on a short jumper in the first half of the N.C. State game on Jan. 12. Walker's short jumper in the lane at the12:51 mark of the first half of the N.C. State game sent her over the 1000-point mark. She had an opportunity to score her 1000th point on a free throw earlier in the game, but missed.
Right On the Money
Prior to the Jan. 30 game vs. Georgia Tech, Kate Mooney had only connected on 18 three-pointers this season. She was 0-10 from the field in the Duke game (Jan. 23) and then went 0-2 in the Old Dominion game (Jan. 27). But in the next three games, Mooney shot .513 (20-39) from the field and led the team in scoring in each of those games. In addition, she was 16-29 (.552) from beyond the arc during that stretch.
She recorded a career-high 20 points in the 93-57 win over Georgia Tech (Jan. 30) and then hit a new career-high of 22 points in the 83-76 overtime win at Florida State (Feb. 1). She continued the barrage with 21 points in the 72-55 win over Clemson (Feb. 5). She is the only player on the current roster to have scored 20 or more points in three consecutive games.
She tied the school record for three-point field goals in a game with seven treys in the Florida State game and tied the school record for three-point field goals in a half with five in the first half against the Seminoles.
Ready to Play
Point guard Renee Robinson, who missed two games due to a concussion, was cleared to play in the Feb. 5 game with Clemson. Robinson suffered the injury in the Old Dominion game (Jan. 27) when she collided with Mery Andrade at midcourt. She was knocked unconscious, but returned to play in that game. However, on the team's return to Charlottesville, Robinson was diagnosed with a concussion and was sidelined for the Georgia Tech game (Jan. 30) and the Florida State game (Feb.1).
Since her return in the Clemson game, Robinson has averaged 15.5 minutes of action, but has not regained her starting role from freshman Erin Stovall.
Breaking Into The Top 10
DeMya Walker has 642 rebounds in her career and ranks ninth in school history. She passed Val Ackerman who had 641 rebounds.
McKinney Named Player of the Week
For the first time this season, a Virginia player was touted as the ACC Player of the Week. Mimi McKinney earned the honor for the week of Jan. 19 after leading Virginia to a 105-100 upset of seventh-ranked North Carolina.
McKinney Makes Mark
Mimi McKinney was scorching the nets on Jan. 15 in Chapel Hill, N.C. and she became the first woman in Virginia history to score over 40 points in a game. She was 16-27 from the field, 7-12 from three-point range and 9-13 from the charity stripe in her 48-point performance against fifth-ranked North Carolina in triple overtime (Jan. 15). She had 35 points at the end of regulation. The 48 points is the most ever by a men's or women's Virginia player against a Division I opponent. McKinney's 48 points ranks second all-time in Virginia basketball history behind Barry Parkhill's 51 points vs. Baldwin-Wallace (Dec. 11, 1971) and ties Buzzy Wilkerson's 48-point game vs. Hampden-Sydney (Dec. 1, 1954).
She eclipsed the women's single game scoring record of 39 established by Wendy Palmer in the Maryland game on Jan. 25, 1995.
Climbing Up The Charts
Mimi McKinney and Kate Mooney are moving up the chart in three-point shooting. McKinney's seven treys against UNC moved her ahead of Mooney.
Tora Suber is Virginia's all-time leader in three-point field goals
made with 220.
Player G Made Att.
1. Tora Suber 127 220 666
2. Tammi Reiss 127 139 334
3. Dena Evans 134 129 370
4. Dawn Staley 131 124 371
5. Monick Foote 84 121 326
6. Mimi McKinney 98 87 269
7. Kate Mooney 75 84 259
8. Kathy McConnell 62 64 210
9. Donna Holt 32 49 128
10. Wendy Palmer 126 31 96
Walker Is UVa's All-Time Blocks Leader
DeMya Walker set a new UVa single game record for blocked shots with eight blocks in the Florida State game on Jan. 2. She broke the old record of seven which was held by Walker (twice), Heidi Burge and Jacki LaBerge. she ranks fifth in ACC history in blocked shots.
Walker's first block of the season, which came in the 13:06 mark in the second half of the William & Mary game (Nov. 16), established her as the Virginia's all-time blocks leader, eclipsing the mark of 152 set by Heather Burge (1990-93). Walker ended the night with three blocks.
Walker Second in Nation in Blocks
DeMya Walker ranks second in the nation in blocked shots. Samantha Tomlinson of Troy State is top shot blocker in the country with 4.1 blocks per game. Here are the top five in that category:
player (school) G B Avg.
1. Samantha Tomlinson (Troy St.) 21 88 4.1
2. DeMya Walker (Virginia) 24 82 3.3
Teresa Jenkins (Florida A & M) 21 68 3.2
4. Myndee Larsen (Southern Utah) 21 64 3.0
5. Brooke Wyckoff (Florida State) 23 69 3.0
Walker Fourth in ACC Blocks
Walker is closing in on the ACC numbers as well. Currently, she ranks fourth in the conference in blocked shots with 234 career blocked shots.
player, school (years) G B Avg.
1. Dawn Royster, UNC (1984-87) 110 329 3.0
2. Peggy Caple, Clem (1982-1985) 119 298 2.5
3. Dolores Bootz, GaT (1985-88) 91 245 2.7
4. DeMya Walker, Va. (1996- present) 88 234 2.7
ACC Season-Highs
Mimi McKinney's 48 points vs. North Carolina is the ACC's season high in points. She also holds the season-high in field goals made (16) and three-point field goals made (7). DeMya Walker's eight blocks is a season-high for the conference, tied with Florida State's Brooke Wyckoff.
As a team, Virginia has achieved the league high in four categories: field goal percentage defense (.183 vs. Mt. St. Mary's), steals (25 vs. California), blocks (14, vs. Mt. St. Mary's).
UVA Athletics Information
In the NewsRecent Headlines News Archives
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Jeff White
Margin of Error Gone for CavaliersMen's Lacrosse4/29/16To become eligible for an NCAA men's lacrosse tournament bid, Virginia (7-7) must upset second-ranked Brown (13-1) on Saturday night.UVA Spring Football NotebookFootball4/27/16With spring practice over, Virginia head coach Bronco Mendenhall and his assistants have turned their focus to recruiting.Cavaliers Push On With Heavy HeartsBaseball4/25/16No. 21 Virginia, coming off an emotionally draining weekend in Coral Gables, Fla., meets ODU at noon Tuesday in Norfolk at Harbor Park.
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A 1985 graduate of UVA, White worked at the Richmond Times-Dispatch until July 2009. He was honored six times as the state's Sportswriter of the Year.
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Archived Story
NHS girls fall in tourney title gamePublished 12:40pm Monday, December 24, 2012
PINETOWN — A cold December night got a little extra chilly inside the Northside High School gym as the Panthers offense went frigid during their 61-41 loss to Currituck in the championship game of the Northside Christmas tournament on Saturday.
"We were a little cold tonight because some of our players didn't play (Friday night)," Northside coach Michelle Leathers said. "We didn't defend like we normally defend and we didn't knock down our free throws. I don't know how many free throws we missed but that was a big difference in the game."
The Panthers kept pace with Currituck early as a late bucket by Alex Adams gave them a 13-11 lead at the end of the first quarter.
Adams would score again to start the second and put the team up 15-11, but the tide turned when center Jordan Woolard got into early foul trouble.
The Lady Knights exploited Northside in the paint as center Kayla Powell scored seven of her game-high 20 points in the second quarter as Currituck went on a 13-3 run that put it ahead 24-18 after an Amanda Gerni three.
"That was kind of the turning point when (Woolard) got in foul trouble," Northside coach Michelle Leathers said. "She just had a bit of a mental breakdown and got in foul trouble. She felt like she couldn't defend how she wanted."
Northside went into halftime down 29-21 but its offense bogged down in the third as it managed only six points in eight minutes. As a result, the Panthers opened up the fourth quarter trailing 40-27.
The Panthers offense flickered at times in the fourth but could not burn bright enough to take down the Knights.
Some key baskets by Adams and forward Kelsey Lang cut the Lady Knights lead to 46-35 with six minutes to go but Currituck clamped down to win the tourney title.
Leathers praised the effort of Lang after the game.
"Lang came in and hit a few big shots and I've been getting on her to take some more shots," Leathers said. "We just have to keep defending and playing hard."
Currituck 11 18 11 21 — 61
Northside 13 8 6 14 — 41
Lady Knights (61)
Kayla Powell 20, Megan Sample 10, Matulewitz 9, Amanda Gerni 14, Owens 4, Harlow 1.
Panthers (41)
Alex Adams 10, Franks 4, Slade 7, Lang 7, Clark 2, Woolard 7, Whitney 1, Holmes 2.


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de Repentigny, L
Infection and Immunity
Oral candidiasis is a common fungal infection in patients infected with the human immunodeficiency virus (HIV). Although rare at the time of primary HIV infection, it is frequently found throughout the asymptomatic phase and is predictive of progressive immunodeficiency. However, the precise immune defect which results in outgrowth of commensal Candida albicans in HIV infection has not been identified. Mice infected with the Du5H(G6T2) mixture of mouse leukemia viruses develop a syndrome, designated murine AIDS (MAIDS), that has many of the immune abnormalities found in HIV infection. Retrovirus-infected C57BL/6 mice were examined for their ability to resist the development of oral candidiasis from the carrier state established after a self-limiting acute infection and to clear a subsequent secondary inoculum of oral C. albicans. Most of the mice orally colonized with C. albicans and then inoculated with the retrovirus mixture maintained a low-level oral carriage of C. albicans, while 30% of coinfected mice developed recurring 2- to 3-week episodes of acute Candida proliferation, separated by transient recoveries to the carrier state. The frequencies of CD4+ and CD8+ lymphocytes were, respectively, unchanged and significantly decreased (P < 0.05) in both cervical lymph nodes and spleens of coinfected mice compared to the corresponding frequencies in C. albicans-carrying, virus-free, age-matched control animals. Secretion of gamma interferon by concanavalin A (ConA)-stimulated spleen cells from Candida-carrying, retrovirus-infected mice was significantly decreased (P < 0.05) compared to that of C. albicans-carrying, retrovirus-free mice, in accordance with known abnormalities associated with MAIDS. However, production of this cytokine by ConA-stimulated or unstimulated cervical lymph node cells from coinfected mice was enhanced compared to that of virus-free animals colonized with C. albicans. Acquired resistance to reinfection with C. albicans was maintained in retrovirus-infected mice and was associated with a mucosal recruitment of CD8+ cells not observed in control mice. These results suggest that alterations in mucosal immunity which occur in MAIDS differ substantially from defects observed at other sites and that surrogate epithelial defense mechanisms may function locally to limit Candida proliferation.
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Local Production of Chemokines during Experimental Vaginal Candidiasis
Saavedra, Michael
Taylor, Brad
Lukacs, Nicholas
Fidel, Paul L.
Infection and Immunity
Recurrent vulvovaginal candidiasis, caused by Candida albicans, is a significant problem in women of childbearing age. Although cell-mediated immunity (CMI) due to T cells and cytokines is the predominant host defense mechanism against C. albicans at mucosal tissue sites, host defense mechanisms against C. albicans at the vaginal mucosa are poorly understood. Based on an estrogen-dependent murine model of vaginal candidiasis, our data suggest that systemic CMI is ineffective against C. albicans vaginal infections. Thus, we have postulated that local immune mechanisms are critical for protection against infection. In the present study, the kinetic production of chemokines normally associated with the chemotaxis of T cells, macrophages (RANTES, MIP-1α, MCP-1), and polymorphonuclear neutrophils (MIP-2) was examined following intravaginal inoculation of C. albicans in estrogen-treated or untreated mice. Results showed significant increases in MCP-1 protein and mRNA in vaginal tissue of infected mice as early as 2 and 4 days postinoculation, respectively, that continued through a 21-day observation period, irrespective of estrogen status. No significant changes were observed with RANTES, MIP-1α, or MIP-2, although relatively high constitutive levels of RANTES mRNA and MIP-2 protein were observed. Furthermore, intravaginal immunoneutralization of MCP-1 with anti-MCP-1 antibodies resulted in a significant increase in vaginal fungal burden early during infection, suggesting that MCP-1 plays some role in reducing the fungal burden during vaginal infection. However, the lack of changes in leukocyte profiles in vaginal lavage fluids collected from infected versus uninfected mice suggests that MCP-1 functions to control vaginal C. albicans titers in a manner independent of cellular chemotactic activity.
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Candida albicans forms biofilms on the vaginal mucosa
Harriott, M. M.
Lilly, E. A.
Rodriguez, T. E.
Fidel, P. L.
Noverr, M. C.
2010;156(Pt 12):3635-3644.
Current understanding of resistance and susceptibility to vulvovaginal candidiasis challenges existing paradigms of host defence against fungal infection. While abiotic biofilm formation has a clearly established role during systemic Candida infections, it is not known whether C. albicans forms biofilms on the vaginal mucosa and the possible role of biofilms in disease. In vivo and ex vivo murine vaginitis models were employed to examine biofilm formation by scanning electron and confocal microscopy. C. albicans strains included 3153A (lab strain), DAY185 (parental control strain), and mutants defective in morphogenesis and/or biofilm formation in vitro (efg1/efg1 and bcr1/bcr1). Both 3153A and DAY815 formed biofilms on the vaginal mucosa in vivo and ex vivo as indicated by high fungal burden and microscopic analysis demonstrating typical biofilm architecture and presence of extracellular matrix (ECM) co-localized with the presence of fungi. In contrast, efg1/efg1 and bcr1/bcr1 mutant strains exhibited weak or no biofilm formation/ECM production in both models compared to wild-type strains and complemented mutants despite comparable colonization levels. These data show for the first time that C. albicans forms biofilms in vivo on vaginal epithelium, and that in vivo biotic biofilm formation requires regulators of biofilm formation (BCR1) and morphogenesis (EFG1).
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Candida-specific Th1-type responsiveness in mice with experimental vaginal candidiasis.
Fidel, P L
Lynch, M E
Sobel, J D
Infection and Immunity
The role of systemic cell-mediated immunity (CMI) as a host defense mechanism in the vagina is poorly understood. Using a murine pseudoestrus model of experimental vaginal candidiasis, we previously found that animals given a vaginal inoculum of viable Candida albicans blastoconidia acquired a persistent vaginal infection and developed Candida-specific delayed-type hypersensitivity (DTH) responses. The present study was designed to characterize the peripheral CMI reactivity generated from the vaginal infection in mice and to determine whether pseudoestrus is a prerequisite for the induction of peripheral CMI reactivity. Mice treated or not treated with estrogen and given a vaginal inoculum of C. albicans blastoconidia were examined for 4 weeks for their vaginal Candida burden and peripheral CMI reactivity, including DTH responsiveness and in vitro Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma]/Th2 (IL-4, IL-10)-type lymphokine production in response to Candida antigens. Results showed that although mice not treated with estrogen before being given a vaginal inoculum of C. albicans blastoconidia developed only a short-lived vaginal infection and harbored significantly fewer Candida CFU in the vagina compared with those given estrogen and then infected; DTH reactivity was equivalent in both groups. In vitro measurement of CMI reactivity further showed that lymph node cells from both estrogen- and non-estrogen-treated infected mice produced elevated levels of IL-2 and IFN-gamma in response to Candida antigens during the 4 weeks after vaginal inoculation. In contrast, lymph node cells from the same vaginally infected mice showed no IL-10 production and only small elevations of IL-4 during week 4 of infection. These results suggest that mice with experimental vaginal candidiasis develop predominantly Th1-type Candida-specific peripheral CMI reactivity and that similar patterns of Th1-type reactivity occur in mice regardless of the persistence of infection and the estrogen status of the infected mice.
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Candida-Specific Antibodies during Experimental Vaginal Candidiasis in Mice
Wozniak, Karen L.
Wormley, Floyd L.
Fidel, Paul L.
Infection and Immunity
Protective host defense mechanisms against vaginal Candida albicans infections are poorly understood. Although cell-mediated immunity (CMI) is the predominant host defense mechanism against most mucosal Candida infections, the role of CMI against vaginal candidiasis is uncertain, both in humans and in an experimental mouse model. The role of humoral immunity is equally unclear. While clinical observations suggest a minimal role for antibodies against vaginal candidiasis, an experimental rat model has provided evidence for a protective role for Candida-specific immunoglobulin A (IgA) antibodies. Additionally, Candida vaccination-induced IgM and IgG3 antibodies are protective in a mouse model of vaginitis. In the present study, the role of infection-induced humoral immunity in protection against experimental vaginal candidiasis was evaluated through the quantification of Candida-specific IgA, IgG, and IgM antibodies in serum and vaginal lavage fluids of mice with primary and secondary (partially protected) infection. In naïve mice, total, but not Candida-specific, antibodies were detected in serum and lavage fluids, consistent with lack of yeast colonization in mice. In infected mice, Candida-specific IgA and IgG antibodies were induced in serum with anamnestic responses to secondary infection. In lavage fluid, while Candida-specific antibodies were detectable, concentrations were extremely low with no anamnestic responses in mice with secondary infection. The incorporation of alternative protocols—including infections in a different strain of mice, prolongation of primary infection prior to secondary challenge, use of different enzyme-linked immunosorbent assay capture antigens, and concentration of lavage fluid—did not enhance local Candida-specific antibody production or detection. Additionally, antibodies were not removed from lavage fluids by being bound to Candida during infection. Together, these data suggest that antibodies are not readily present in vaginal secretions of infected mice and thus have a limited natural protective role against infection.
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Effects of preinduced Candida-specific systemic cell-mediated immunity on experimental vaginal candidiasis.
Fidel, P L
Lynch, M E
Sobel, J D
Infection and Immunity
It has been postulated that systemic cell-mediated immunity (CMI) is an important host defense factor against recurrent vaginal infections caused by Candida albicans. Using an estrogen-dependent murine model of vaginal candidiasis, we have previously shown that mice inoculated vaginally with C. albicans acquire a persistent vaginal infection and develop Candida-specific Th1-type systemic CMI. In the present study, experimental vaginitis was monitored in the presence of preinduced systemic Candida-specific CMI. Mice immunized systemically with C. albicans culture filtrate antigens (CaCF) in complete Freund's adjuvant (CFA) had Th1-type reactivity similar to that of vaginally infected mice. CaCF given to mice intravenously induced Candida-specific suppressor T (Ts) cells. Mice preimmunized with CaCF-CFA and given a vaginal inoculum of C. albicans had positive delayed-type hypersensitivity (DTH) reactivity from the time of vaginal inoculation through 4 weeks. Conversely, mice infected in the presence of Ts cells had significantly reduced DTH responses throughout the 4-week period in comparison with naive infected mice. However, the presence of Th1-type Candida-specific DTH cells or Ts cells, either induced in mice prior to vaginal inoculation or adoptively transferred at the time of inoculation, had no effect on the vaginal Candida burden through 4 weeks of infection. A similar lack of effects was obtained in animals with lower Candida population levels resulting from a reduction in or absence of exogenous estrogen. These results suggest that systemic Th1-type CMI demonstrable with CaCF is unrelated to protective events at the level of the vaginal mucosa.
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The Secreted Aspartyl Proteinases Sap1 and Sap2 Cause Tissue Damage in an In Vitro Model of Vaginal Candidiasis Based on Reconstituted Human Vaginal Epithelium
Schaller, Martin
Bein, Matthias
Korting, Hans C.
Baur, Stefan
Hamm, Gerald
Monod, Michel
Beinhauer, Sabine
Hube, Bernhard
Infection and Immunity
Secreted aspartyl proteinases (Saps) contribute to the ability of Candida albicans to cause mucosal and disseminated infections. A model of vaginal candidiasis based on reconstituted human vaginal epithelium (RHVE) was used to study the expression and role of these C. albicans proteinases during infection and tissue damage of vaginal epithelium. Colonization of the RHVE by C. albicans SC5314 did not cause any visible epithelial damage 6 h after inoculation, although expression of SAP2, SAP9, and SAP10 was detected by reverse transcriptase PCR. However, significant epithelial damage was observed after 12 h, concomitant with the additional expression of SAP1, SAP4, and SAP5. Additional transcripts of SAP6 and SAP7 were detected at a later stage of the artificial infection (24 h). Similar SAP expression profiles were observed in three samples isolated from human patients with vaginal candidiasis. In experimental infection, secretion of antigens Sap1 to Sap6 by C. albicans was confirmed at the ultrastructural level by using polyclonal antisera raised against Sap1 to Sap6. Addition of the aspartyl proteinase inhibitors pepstatin A and the human immunodeficiency virus proteinase inhibitors ritonavir and amprenavir strongly reduced the tissue damage of the vaginal epithelia by C. albicans cells. Furthermore, SAP null mutants lacking either SAP1 or SAP2 had a drastically reduced potential to cause tissue damage even though SAP3, SAP4, and SAP7 were up-regulated in these mutants. In contrast the vaginopathic potential of mutants lacking SAP3 or SAP4 to SAP6 was not reduced compared to wild-type cells. These data provide further evidence for a crucial role of Sap1 and Sap2 in C. albicans vaginal infections.
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High Aspartyl Proteinase Production and Vaginitis in Human Immunodeficiency Virus-Infected Women
de Bernardis, F.
Mondello, F.
Scaravelli, G.
Pachì, A.
Girolamo, A.
Agatensi, L.
Cassone, A.
Journal of Clinical Microbiology
Vaginal isolates of Candida albicans from human immunodeficiency virus-positive (HIV+) and HIV− women with or without candidal vaginitis were examined for secretory aspartyl proteinase (Sap) production in vitro and in vivo and for the possible correlation of Sap production with pathology and antimycotic susceptibility in vitro. HIV+ women with candidal vaginitis were infected by strains of C. albicans showing significantly higher levels of Sap, a virulence enzyme, than strains isolated from HIV+, C. albicans carrier subjects and HIV− subjects with vaginitis. The greater production of Sap in vitro was paralleled by greater amounts of Sap in the vaginal fluids of infected subjects. In an estrogen-dependent, rat vaginitis model, a strain of C. albicans producing a high level of Sap that was isolated from an HIV+ woman with vaginitis was more pathogenic than a strain of C. albicans that was isolated primarily from an HIV−, Candida carrier. In the same model, pepstatin A, a strong Sap inhibitor, exerted a strong curative effect on experimental vaginitis. No correlation was found between Sap production and antimycotic susceptibility, as most of the isolates were fully susceptible to fluconazole, itraconazole, and other antimycotics, regardless of their source (subjects infected with strains producing high or low levels of Sap, subjects with vaginitis or carrier subjects, or subjects with or without HIV). Thus, high Sap production is associated with virulence of C. albicans but not with fungal resistance to fluconazole in HIV-infected subjects, and Sap is a potentially new therapeutic target in candidal vaginitis.
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Expression of Candida albicans SAP1 and SAP2 in experimental vaginitis.
De Bernardis, F
Cassone, A
Sturtevant, J
Calderone, R
Infection and Immunity
Several strains of Candida albicans were compared for their ability to cause vaginal infection in a rat model, and their vaginopathic potentials were correlated with the expression of two aspartyl proteinases genes (SAP1 and SAP2) and adherence in vivo to the vaginal epithelium. Dot blot reactions and Northern blot analysis with RNA extracted from the vaginal fluid of rats infected with the highly vaginopathic strains H12 and 10261 demonstrated the expression of both SAP1 and SAP2 during the first week of infection. In contrast, neither gene was expressed during infection by a nonvaginopathic strain (N), even though the organism could be recovered during the first 24 h postinfection. A moderately vaginopathic strain (P) also expressed both genes, but the level of SAP1 mRNA appeared to decrease prior to that of SAP2. Neither gene was expressed, even by the highly vaginopathic strains, after the first week of infection, concomitant with a decrease in the number of organisms recovered from the vaginas. Analysis of in vivo adherence showed that the nonvaginopathic strain (N) adhered to vaginal epithelial cells less readily than the highly vaginopathic strain (H12) and moderately vaginopathic strain (P). Thus, in addition to its inability to express SAP1 and SAP2 in vivo, the nonvaginopathic strain does not colonize host cells to the same extent as the other strains tested. Our results demonstrate the early in vivo expression of two aspartyl proteinase gene during candidal vaginitis and suggest its association with the establishment of a vaginal infection.
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Interplay between the Gastric Bacterial Microbiota and Candida albicans during Postantibiotic Recolonization and Gastritis
Mason, Katie L.
Erb Downward, John R.
Falkowski, Nicole R.
Young, Vincent B.
Kao, John Y.
Huffnagle, Gary B.
Infection and Immunity
The indigenous bacterial microbiome of the stomach, including lactobacilli, is vital in promoting colonization resistance against Candida albicans. However, there are gaps in our understanding about C. albicans gastric colonization versus disease, especially during the postantibiotic recovery phase. This study compared the gastric responses to C. albicans strains CHN1 and SC5314 in microbiome-disturbed and germfree mice to elucidate the contribution of the indigenous microbiota in C. albicans colonization versus disease and yeast-bacterium antagonism during the post-cefoperazone recolonization period. C. albicans can prevent the regrowth of Lactobacillus spp. in the stomach after cefoperazone and promote increased colonization by Enterococcus spp. Using a culture-independent analysis, the effects of oral cefoperazone on the gastric bacterial microbiota were observed to last at least 3 weeks after the cessation of the antibiotic. Disturbance of the gastric bacterial community by cefoperazone alone was not sufficient to cause gastritis, C. albicans colonization was also needed. Gastritis was not evident until after day 7 in cefoperazone-treated infected mice. In contrast, in germfree mice which lack a gastric microbiota, C. albicans induced gastric inflammation within 1 week of inoculation. Therefore, the gastric bacterial community in cefoperazone-treated mice during the first week of postantibiotic recolonization was sufficient to prevent the development of gastritis, despite being ineffective at conferring colonization resistance against C. albicans. Altogether, these data implicate a dichotomy between C. albicans colonization and gastric disease that is bacterial microbiome dependent.
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Candida albicans-Secreted Aspartic Proteinases Modify the Epithelial Cytokine Response in an In Vitro Model of Vaginal Candidiasis
Schaller, Martin
Korting, Hans C.
Borelli, Claudia
Hamm, Gerald
Hube, Bernhard
Infection and Immunity
Secreted aspartyl proteinases (Saps) are important virulence factors of Candida albicans during mucosal and disseminated infections and may also contribute to the induction of an inflammatory host immune response. We used a model of vaginal candidiasis based on reconstituted human vaginal epithelium (RHVE) to study the epithelial cytokine response induced by C. albicans. In order to study the impact of the overall proteolytic activity and of distinct Sap isoenzymes, we studied the effect of the proteinase inhibitor pepstatin A on the immune response and compared the cytokine expression pattern induced by the wild-type strain SC5314 with the pattern induced by Sap-deficient mutants. Infection of RHVE with the C. albicans wild-type strain induced strong interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, gamma interferon, and tumor necrosis factor alpha responses in comparison with cytokine expression in noninfected tissue. Addition of the aspartyl proteinase inhibitor pepstatin A strongly reduced the cytokine response of RHVE. Furthermore, SAP-null mutants lacking either SAP1 or SAP2 caused reduced tissue damage and had a significantly reduced potential to stimulate cytokine expression. In contrast, the vaginopathic and cytokine-inducing potential of mutants lacking SAP4 to SAP6 was similar to that of the wild-type strain. These data show that the potential of specific Saps to cause tissue damage correlates with an epithelium-induced proinflammatory cytokine response, which may be crucial in controlling and managing C. albicans infections at the vaginal mucosa in vivo.
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Using Bayesian modelling to investigate factors governing antibiotic-induced Candida albicans colonization of the GI tract
Shankar, Jyoti
Solis, Norma V.
Mounaud, Stephanie
Szpakowski, Sebastian
Liu, Hong
Losada, Liliana
Nierman, William C.
Filler, Scott G.
Scientific Reports
Receipt of broad-spectrum antibiotics enhances Candida albicans colonization of the GI tract, a risk factor for haematogenously-disseminated candidiasis. To understand how antibiotics influence C. albicans colonization, we treated mice orally with vancomycin or a combination of penicillin, streptomycin, and gentamicin (PSG) and then inoculated them with C. albicans by gavage. Only PSG treatment resulted in sustained, high-level GI colonization with C. albicans. Furthermore, PSG reduced bacterial diversity in the colon much more than vancomycin. Both antibiotic regimens significantly reduced IL-17A, IL-21, IL-22 and IFN-γ mRNA levels in the terminal ileum but had limited effect on the GI fungal microbiome. Through a series of models that employed Bayesian model averaging, we investigated the associations between antibiotic treatment, GI microbiota, and host immune response and their collective impact on C. albicans colonization. Our analysis revealed that bacterial genera were typically associated with either C. albicans colonization or altered cytokine expression but not with both. The only exception was Veillonella, which was associated with both increased C. albicans colonization and reduced IL-21 expression. Overall, antibiotic-induced changes in the bacterial microbiome were much more consistent determinants of C. albicans colonization than either the GI fungal microbiota or the GI immune response.
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Horizontal Transmission of Candida albicans and Evidence of a Vaccine Response in Mice Colonized with the Fungus
Cutler, Jim E.
Corti, Miriam
Lambert, Patrick
Ferris, Michael
Xin, Hong
PLoS ONE
Disseminated candidiasis is the third leading nosocomial blood stream infection in the United States and is often fatal. We previously showed that disseminated candidiasis was preventable in normal mice by immunization with either a glycopeptide or a peptide synthetic vaccine, both of which were Candida albicans cell wall derived. A weakness of these studies is that, unlike humans, mice do not have a C. albicans GI flora and they lack Candida serum antibodies. We examined the influence of C. albicans GI tract colonization and serum antibodies on mouse vaccination responses to the peptide, Fba, derived from fructose bisphosphate aldolase which has cytosolic and cell wall distributions in the fungus. We evaluated the effect of live C. albicans in drinking water and antimicrobial agents on establishment of Candida colonization of the mouse GI tract. Body mass, C. albicans in feces, and fungal-specific serum antibodies were monitored longitudinally. Unexpectedly, C. albicans colonization occurred in mice that received only antibiotics in their drinking water, provided that the mice were housed in the same room as intentionally colonized mice. The fungal strain in unintentionally colonized mice appeared identical to the strain used for intentional GI-tract colonization. This is the first report of horizontal transmission and spontaneous C. albicans colonization in mice. Importantly, many Candida-colonized mice developed serum fungal-specific antibodies. Despite the GI-tract colonization and presence of serum antibodies, the animals made antibodies in response to the Fba immunogen. This mouse model has potential for elucidating C. albicans horizontal transmission and for exploring factors that induce host defense against disseminated candidiasis. Furthermore, a combined protracted GI-tract colonization with Candida and the possibility of serum antibody responses to the presence of the fungus makes this an attractive mouse model for testing the efficacy of vaccines designed to prevent human disseminated candidiasis.
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Mucosal Damage and Neutropenia Are Required for Candida albicans Dissemination
Koh, Andrew Y
Köhler, Julia R
Coggshall, Kathleen T
Van Rooijen, Nico
Pier, Gerald B
PLoS Pathogens
Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI) colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for allowing widespread invasive C. albicans disease. We investigated these parameters in a mouse model of C. albicans GI colonization that led to systemic spread after administration of immunosuppression and mucosal damage. After depleting resident GI intestinal flora with antibiotic treatment and achieving stable GI colonization levels of C. albicans, it was determined that systemic chemotherapy with cyclophosphamide led to 100% mortality, whereas selective neutrophil depletion, macrophage depletion, lymphopenia or GI mucosal disruption alone resulted in no mortality. Selective neutrophil depletion combined with GI mucosal disruption led to disseminated fungal infection and 100% mortality ensued. GI translocation and dissemination by C. albicans was also dependent on the organism's ability to transform from the yeast to the hyphal form. This mouse model of GI colonization and fungemia is useful for studying factors of innate host immunity needed to prevent invasive C. albicans disease as well as identifying virulence factors that are necessary for fungal GI colonization and dissemination. The model may also prove valuable for evaluating therapies to control C. albicans infections.
Author Summary
Candida albicans is a fungus that lives harmlessly in the gastrointestinal (GI) tracts of humans. In cancer patients and patients undergoing bone marrow transplantation, however, the anti-cancer drugs that are administered to these patients also cause the undesired effect of suppressing the human immune system. The treatments allow C. albicans to spread into the blood and other organs and cause a severe disease. We found we could colonize the GI tracts of mice with C. albicans and then suppress the immune system with anti-cancer drugs to determine which components of the innate immune system (neutrophils, lymphocytes, macrophages, or GI tract integrity) are critical for preventing C. albicans from speading from the GI tract. We found that lowering the neutrophil counts and damaging the GI tract were both needed to cause systemic infection with C. albicans. We also found that the ability of C. albicans to switch from the yeast (spherical) form to the filamentous form is also important for establishing invasive disease. Our study provides new insights into the process of how a typically harmless microorganism inhabiting the GI tract can cause severe invasive disease once critical components of the host immune system are compromised.
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Fungal Morphogenetic Pathways Are Required for the Hallmark Inflammatory Response during Candida albicans Vaginitis
Peters, Brian M.
Palmer, Glen E.
Nash, Andrea K.
Lilly, Elizabeth A.
Fidel, Paul L.
Noverr, Mairi C.
Infection and Immunity
Vulvovaginal candidiasis, caused primarily by Candida albicans, presents significant health issues for women of childbearing age. As a polymorphic fungus, the ability of C. albicans to switch between yeast and hyphal morphologies is considered its central virulence attribute. Armed with new criteria for defining vaginitis immunopathology, the purpose of this study was to determine whether the yeast-to-hypha transition is required for the hallmark inflammatory responses previously characterized during murine vaginitis. Kinetic analyses of vaginal infection with C. albicans in C57BL/6 mice demonstrated that fungal burdens remained constant throughout the observation period, while polymorphonuclear leukocyte (PMN), S100A8, and interleukin-1β levels obtained from vaginal lavage fluid increased by day 3 onward. Lactate dehydrogenase activity was also positively correlated with increased effectors of innate immunity. Additionally, immunodepletion of neutrophils in infected mice confirmed a nonprotective role for PMNs during vaginitis. Determination of the importance of fungal morphogenesis during vaginitis was addressed with a two-pronged approach. Intravaginal inoculation of mice with C. albicans strains deleted for key transcriptional regulators (bcr1Δ/Δ, efg1Δ/Δ, cph1Δ/Δ, and efg1Δ/Δ cph1Δ/Δ) controlling the yeast-to-hypha switch revealed a crucial role for morphogenetic signaling through the Efg1 and, to a lesser extent, the Bcr1 pathways in contributing to vaginitis immunopathology. Furthermore, overexpression of transcription factors NRG1 and UME6, to maintain yeast and hyphal morphologies, respectively, confirmed the importance of morphogenesis in generating innate immune responses in vivo. These results highlight the yeast-to-hypha switch and the associated morphogenetic response as important virulence components for the immunopathogenesis of Candida vaginitis, with implications for transition from benign colonization to symptomatic infection.
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Filamentous growth and elevated vaginopathic potential of a nongerminative variant of Candida albicans expressing low virulence in systemic infection.
De Bernardis, F
Adriani, D
Lorenzini, R
Pontieri, E
Carruba, G
Cassone, A
Infection and Immunity
The vaginopathic potential and the intravaginal morphology of a nongerminative variant of Candida albicans, strain CA-2, were studied in a rat vaginitis model. Although it expressed low virulence in systemic infections, strain CA-2 was capable of causing a vaginal infection of the same duration and extent as that obtained in rats challenged with the germ-tube-forming strain C. albicans 3153 from the stock collection or with a fresh clinical isolate of C. albicans from a case of human vaginitis. During the experimental infection, the CA-2 cells did not maintain their yeast morphology but gave rise to single enlarged-elongated elements (1 to 2 days) which grew predominantly as coarse, short, pseudomycelium-like filaments (2 to 3 days) and then as long threads (7 days). These latter filaments were ultimately indistinguishable from the hyphal filaments formed by the germ-tube-forming strains, which, however, initially developed in the vagina by typical germ tube formation. This peculiar morphological development of strain CA-2 was not observed in organs of systemically infected mice, where, in contrast to strain 3153 which formed typical hyphae, strain CA-2 maintained a typical pattern of yeast growth. Vaginal isolates of strain CA-2 taken at different days of infection were found to be identical to the challenging CA-2 cells, in terms of biochemical characteristics, inability to form germ tubes in any medium at 37 degrees C in vitro, echinocandin resistance, DNA biotype, and low virulence in systemic infections in mice. Thus, experimental vaginitis by strain CA-2 is associated with a peculiar filamentous growth in the vagina, through an apparently novel morphological development bypassing classical germ tube formation but ultimately leading to ordinary hyphae. The elevated vaginopathic potential of strain CA-2, in contrast to its low virulence in systemic infection, also suggests that different Candida virulence factors (and host responses) come into play in local and disseminated candidal infections.
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Circulating CD4 and CD8 T cells have little impact on host defense against experimental vaginal candidiasis.
Fidel, P L
Lynch, M E
Sobel, J D
Infection and Immunity
The etiology of recurrent vulvovaginal candidiasis in otherwise healthy women of child-bearing age remains an enigma. To date, results from both clinical studies and a murine model of vaginal candidiasis indicate that Candida vaginitis can occur in the presence of Candida-specific Th1-type cell-mediated immunity expressed in the peripheral circulation. The present study was designed to determine the role of circulating CD4 and CD8 cells in primary and secondary vaginal infections with Candida albicans. Vaginal fungal burden, Candida-specific delayed-type hypersensitivity (DTH), and lymph node cell Th1/Th2 cytokine production were monitored in CD4 and/or CD8 cell-depleted mice during persistent primary vaginal infections and secondary vaginal infections against which partial protection was observed. Treatment of mice with anti-CD4 or anti-CD8 antibodies resulted in 90% or greater depletion of the respective cell populations. Mice depleted of CD4 cells had significantly reduced Candida-specific DTH and lymph node cell Th1-type cytokine production during a primary vaginal infection, as well as reduced anamnestic DTH during a secondary vaginal infection. In contrast, mice depleted of CD8 cells showed only reduced gamma interferon production during a primary infection; no alterations in DTH were observed. Despite reductions in DTH and cytokine production, however, CD4 and/or CD8 cell depletion had no effect on vaginal C. albicans burden in mice after a primary or secondary vaginal inoculation. Taken together, these results suggest that while circulating CD4 and CD8 cells contribute to systemic Candida-specific cell-mediated immunity in vaginally infected mice, neither CD4 nor CD8 circulating T cells appear to provide significant host defenses against C. albicans at the vaginal mucosa.
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Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells
Phan, Quynh T
Myers, Carter L
Fu, Yue
Sheppard, Donald C
Yeaman, Michael R
Welch, William H
Ibrahim, Ashraf S
Edwards, John E
Filler, Scott G
PLoS Biology
Candida albicans is the most common cause of hematogenously disseminated and oropharyngeal candidiasis. Both of these diseases are characterized by fungal invasion of host cells. Previously, we have found that C. albicans hyphae invade endothelial cells and oral epithelial cells in vitro by inducing their own endocytosis. Therefore, we set out to identify the fungal surface protein and host cell receptors that mediate this process. We found that the C. albicans Als3 is required for the organism to be endocytosed by human umbilical vein endothelial cells and two different human oral epithelial lines. Affinity purification experiments with wild-type and an als3Δ/als3Δ mutant strain of C. albicans demonstrated that Als3 was required for C. albicans to bind to multiple host cell surface proteins, including N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. Furthermore, latex beads coated with the recombinant N-terminal portion of Als3 were endocytosed by Chinese hamster ovary cells expressing human N-cadherin or E-cadherin, whereas control beads coated with bovine serum albumin were not. Molecular modeling of the interactions of the N-terminal region of Als3 with the ectodomains of N-cadherin and E-cadherin indicated that the binding parameters of Als3 to either cadherin are similar to those of cadherin–cadherin binding. Therefore, Als3 is a fungal invasin that mimics host cell cadherins and induces endocytosis by binding to N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. These results uncover the first known fungal invasin and provide evidence that C. albicans Als3 is a molecular mimic of human cadherins.
Author Summary
The fungus Candida albicans is usually a harmless colonizer of human mucosal surfaces. In the mouth, it can cause oropharyngeal candidiasis, also called thrush. In hospitalized and immunocompromised patients, C. albicans can enter the blood stream and be carried throughout the body to cause a disseminated infection, which is associated with a mortality rate of up to 40%. The organism invades the epithelial cell lining of the mouth during oropharyngeal candidiasis and invades the endothelial cell lining of the blood vessels during disseminated candidiasis. We discovered that Als3, a protein expressed on the surface of C. albicans, is required for this invasion process. Cadherins on the surface of human cells normally bind other cadherins for adhesion and signaling; however, we found that Als3 also binds to cadherins on endothelial cells and oral epithelial cells, and this binding induces these host cells to take up the fungus. The structure of Als3 is predicted to be quite similar to that of the two cadherins studied, and the parameters of the binding of Als3 to either cadherin are similar to those of cadherin–cadherin binding. These results suggest that Als3 is a functional and structural mimic of human cadherins, and provide new insights into how C. albicans invades host cells.
Als3 aids the invasion of the fungal pathogenCandida albicans into human host cells by mimicking human cadherins to induce endocytosis.
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Niche-Specific Requirement for Hyphal Wall protein 1 in Virulence of Candida albicans
Staab, Janet F.
Datta, Kausik
Rhee, Peter
PLoS ONE
Specialized Candida albicans cell surface proteins called adhesins mediate binding of the fungus to host cells. The mammalian transglutaminase (TG) substrate and adhesin, Hyphal wall protein 1 (Hwp1), is expressed on the hyphal form of C. albicans where it mediates fungal adhesion to epithelial cells. Hwp1 is also required for biofilm formation and mating thus the protein functions in both fungal-host and self-interactions. Hwp1 is required for full virulence of C. albicans in murine models of disseminated candidiasis and of esophageal candidiasis. Previous studies correlated TG activity on the surface of oral epithelial cells, produced by epithelial TG (TG1), with tight binding of C. albicans via Hwp1 to the host cell surfaces. However, the contribution of other Tgs, specifically tissue TG (TG2), to disseminated candidiasis mediated by Hwp1 was not known. A newly created hwp1 null strain in the wild type SC5314 background was as virulent as the parental strain in C57BL/6 mice, and virulence was retained in C57BL/6 mice deleted for Tgm2 (TG2). Further, the hwp1 null strains displayed modestly reduced virulence in BALB/c mice as did strain DD27-U1, an independently created hwp1Δ/Δ in CAI4 corrected for its ura3Δ defect at the URA3 locus. Hwp1 was still needed to produce wild type biofilms, and persist on murine tongues in an oral model of oropharyngeal candidiasis consistent with previous studies by us and others. Finally, lack of Hwp1 affected the translocation of C. albicans from the mouse intestine into the bloodstream of mice. Together, Hwp1 appears to have a minor role in disseminated candidiasis, independent of tissue TG, but a key function in host- and self-association to the surface of oral mucosa.
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Cell Adhesion Molecule and Lymphocyte Activation Marker Expression during Experimental Vaginal Candidiasis
Wormley, Floyd L.
Chaiban, Joseph
Fidel, Paul L.
Infection and Immunity
Cell-mediated immunity by Th1-type CD4+ T cells is the predominant host defense mechanism against mucosal candidiasis. However, studies using an estrogen-dependent murine model of vaginal candidiasis have demonstrated little to no change in resident vaginal T cells during infection and no systemic T-cell infiltration despite the presence of Candida-specific systemic Th1-type responses in infected mice. The present study was designed to further investigate these observations by characterizing T-cell activation and cell adhesion molecule expression during primary and secondary C. albicans vaginal infections. While flow cytometry analysis of activation markers showed some evidence for activation of CD3+ draining lymph node and/or vaginal lymphocytes during both primary and secondary vaginal Candida infection, CD3+ cells expressing the homing receptors and integrins α4β7, αM290β7, and α4β1 in draining lymph nodes of mice with primary and secondary infections were reduced compared to results for uninfected mice. At the local level, few vaginal lymphocytes expressed integrins, with only minor changes observed during both primary and secondary infections. On the other hand, immunohistochemical analysis of vaginal cell adhesion molecule expression showed increases in mucosal addressin cell adhesion molecule 1 and vascular cell adhesion molecule 1 expression during both primary and secondary infections. Altogether, these data suggest that although the vaginal tissue is permissive to cellular infiltration during a vaginal Candida infection, the reduced numbers of systemic cells expressing the reciprocal cellular adhesion molecules may preempt cellular infiltration, thereby limiting Candida-specific T-cell responses against infection.
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A Novel Immune Evasion Strategy of Candida albicans: Proteolytic Cleavage of a Salivary Antimicrobial Peptide
Meiller, Timothy F.
Hube, Bernhard
Schild, Lydia
Shirtliff, Mark E.
Scheper, Mark A.
Winkler, Robert
Ton, Amy
Jabra-Rizk, Mary Ann
PLoS ONE
Oropharyngeal candidiasis is an opportunistic infection considered to be a harbinger of AIDS. The etiologic agent Candida albicans is a fungal species commonly colonizing human mucosal surfaces. However, under conditions of immune dysfunction, colonizing C. albicans can become an opportunistic pathogen causing superficial or even life-threatening infections. The reasons behind this transition, however, are not clear. In the oral cavity, salivary antimicrobial peptides are considered to be an important part of the host innate defense system in the prevention of microbial colonization. Histatin-5 specifically has exhibited potent activity against C. albicans. Our previous studies have shown histatin-5 levels to be significantly reduced in the saliva of HIV+ individuals, indicating an important role for histatin-5 in keeping C. albicans in its commensal stage. The versatility in the pathogenic potential of C. albicans is the result of its ability to adapt through the regulation of virulence determinants, most notably of which are proteolytic enzymes (Saps), involved in tissue degradation. In this study, we show that C. albicans cells efficiently and rapidly degrade histatin-5, resulting in loss of its anti-candidal potency. In addition, we demonstrate that this cellular activity is due to proteolysis by a member of the secreted aspartic proteases (Sap) family involved in C. albicans pathogenesis. Specifically, the proteolysis was attributed to Sap9, in turn identifying histatin-5 as the first host-specific substrate for that isoenzyme. These findings demonstrate for the first time the ability of a specific C. albicans enzyme to degrade and deactivate a host antimicrobial peptide involved in the protection of the oral mucosa against C. albicans, thereby providing new insights into the factors directing the transition of C. albicans from commensal to pathogen, with important clinical implications for alternative therapy. This report characterizes the first defined mechanism behind the enhanced susceptibility of HIV+ individuals to oral candidiasis since the emergence of HIV.
Related Articles
In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon.
Garner, R. E.
Kuruganti, U.
Czarniecki, C. W.
Chiu, H. H.
Domer, J. E.
Infection and Immunity
The immunologic effects of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) were determined in a murine model of candidiasis. Naive mice were given graded doses of rMuIFN-gamma and then challenged intravenously with Candida albicans. Increased morbidity and mortality were noted in four different strains of mice, viz., BALB/c, A/J, Swiss Webster, and CBA/J, providing the mice had not been immunized with C. albicans before challenge. Quantitative culture of selected organs of Swiss Webster and CBA/J mice surviving treatment with rMuIFN-gamma revealed elevated numbers of C. albicans cells, particularly in the kidneys, but also in the liver, lungs, and spleen. The lungs, livers, and spleen of female CBA/J mice were more protected from increased multiplication of the fungus than were those of males of the same species or female Swiss Webster mice. On the basis of these initial findings, the effect of treatment with 5,000 U of rMuIFN-gamma on immune responses in a gastrointestinal model of candidiasis was determined. CBA/J mice that had been colonized with C. albicans as infants were boosted with a cutaneous inoculation of the fungus when 6 to 10 weeks old; development of delayed hypersensitivity (DH), antibodies, and protective responses was assayed at intervals thereafter. Daily treatment with rMuIFN-gamma (beginning 1 day before cutaneous inoculation) suppressed weak immune responses but had little effect on responses which were strong. For example, DH and anti-C. albicans antibody production were suppressed in animals colonized with C. albicans but not boosted by cutaneous inoculation, and DH was suppressed in uncolonized animals that had been inoculated once cutaneously with the fungus as well. There was no rMuIFN-gamma-induced suppressive effect of DH in mice which had been stimulated maximally with C. albicans, i.e., colonized animals that had been boosted cutaneously with the organisms. Collectively, these data indicate that naive mice or mice with minimal levels of anti-C. albicans sensitivity, females somewhat more so than males, were sensitive to suppressive effects of in vivo treatment with rMuIFN-gamma when challenged with C. albicans. In contrast, under conditions similar to those of humans, in whom underlying immunity to C. albicans is usually present, suppression of host responses to C. albicans was not observed in immunized mice in response to treatment with rMuIFN-gamma.
Related Articles
Susceptibility of Germfree Phagocyte Oxidase- and Nitric Oxide Synthase 2-Deficient Mice, Defective in the Production of Reactive Metabolites of Both Oxygen and Nitrogen, to Mucosal and Systemic Candidiasis of Endogenous Origin
Balish, Edward
Warner, Thomas F.
Nicholas, Peter J.
Paulling, Emily E.
Westwater, Caroline
Schofield, David A.
Infection and Immunity
Mice deficient for phagocyte oxidase (Phox) and nitric oxide synthase 2 (NOS2) (gp91phox−/−/NOS2−/−), defective in the production of both reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI), were used to investigate the role of phagocytic cells during mucosal and systemic candidiasis of endogenous origin. The alimentary tracts of germfree mice were colonized with Candida albicans wild type or each of two hyphal signaling-defective mutants (efg1/efg1 and efg1/efg1 cph1/cph1). All Candida-colonized gp91phox−/−/NOS2−/− mice were moribund within 12 to 15 days after oral inoculation. C. albicans wild-type and mutant strains colonized the alimentary tracts equally well and were able to translocate, most likely via Peyer's patches and mesenteric lymph nodes, to the internal organs and trigger the formation of abscesses; however, the wild-type and mutant strains did not survive in the abscessed murine tissues. Surprisingly, there was no significant difference in the ability of peritoneal exudate cells from gp91phox−/−/NOS2−/−, NOS2−/−, gp91phox−/−, or immunocompetent C57BL/6 mice to kill C. albicans in vitro. This suggests that anti-Candida factors other than ROI and RNI can control the growth of C. albicans and that gp91phox−/−/NOS2−/− mice die due to the inability of the host to control its inflammatory response to Candida. Correspondingly, reverse transcription-PCR analysis showed increased expression of the cytokines gamma interferon, tumor necrosis factor alpha, and the chemokines MIP-2 and KC at the site of infection, while interleukin-15 expression remained relatively unchanged between germfree and infected tissues. These studies indicate that defects in ROI and RNI enabled C. albicans to translocate and disseminate to the internal organs, resulting in an uncontrolled immune response, severe pathology, and death; however, ROI and RNI were not required for the killing of phagocytized C. albicans, indicating that other anti-Candida factors either compensate or are sufficient for the killing of phagocytized Candida.
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Team Associated Pre-Mounted Front Spoked Wheel & Tire Set (2) (Black)
This is a set of two Team Associated Pre-Mounted Front Tires, and are intended for use with the Team Associated RC18B/T 1/18 scale vehicles. These black spoked narrow front wheels feature Mini-Pin tires and come fully assembled and glued.
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Aggressive best case, per SPWR CC. Second facility at full capacity by beginning of 2008. Total capacity = 300MW/yr. Revenue for 2008 = $1B. P/S for a non-cyclical, rapidly growing market: 5. Total market cap = $5B. Discount factor to get to current $2.15B market cap in excess of 30% per year over three years (through this date in 2009).Rosy, but not out of the question.Simple Simon
Backlog is a whopping $700 millions.10% pricing premium than the peers due to higher conversion efficiency. Will reach 22% by the end of year while industry average is 15%.Wafer useage seems to drop to 8-9 gram/watt, competitive against the best - 8.5 from ESLR.Fails to elaborate why gross margin stays lousy - 19% compared against STP and Q-cell's 32%. Does 19% partly compensate the fab setup cost? How is the trend to improve it? SPWR didn't mention this crtical issue.


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All the latest from Crime
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Man Who Fled Fargo Halfway House Reaches Plea DealA Minnesota man who walked away from a Fargo halfway house has reached a plea agreement with prosecutors. Chad Sumner is charged in federal court with escape.
2 Teens Injured In St. Paul Shooting Police in St. Paul say two teenagers are recovering after being shot late Saturday night.
FBI Offers Reward For Info On Brooklyn Center Bank RobberBrooklyn Center police want the public's help to track down a woman who robbed a bank last week. They believe she was involved in a robbery at a Wells Fargo Bank on Tuesday, April 19 at about 5 p.m.
Anoka Man, 30, Charged In String Of RobberiesA 30-year-old Anoka man has been arrested and charged in connection to a string of robberies north of the metro area, according to the Anoka County Attorney's Office.
St. Paul Man Pleads Guilty To Illegal Gun DealingA St. Paul man has pleaded guilty to illegally selling firearms, several of which are tied to criminal activity. The U.S. Attorney's Office says Eitan Benjamin Feldman, 29, would buy firearms from an online dealer and then sell them on another website for a profit.
Broad Cuts To Drug Sentences Put Minn. Legislature On NoticeMinnesota county attorneys and law enforcement officials say they've reached a deal to make broad reductions to prison sentences for drug offenders.
Fargo Man Pleads Not Guilty In Meth ConspiracyA Fargo man is accused in federal court of selling large quantities of methamphetamine. Joshua Young has pleaded not guilty to conspiracy to possess with intent to distribute a controlled substance. The charge carries a maximum penalty of life in prison without parole.
New Documents Filed In Fight Over Prince's Estate; Search Warrant SealedA judge has approved the Carver County sheriff's request to seal the search warrant and any accompanying documents surrounding investigations into the death of pop superstar Prince.
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3 Reviews
The dough was very wet for these biscuits at our high altitude. The cinnamon wasn't noticeable enough for my kids. If I make these again, I will lower the wet and raise the cinnamon. Still, not a bad treat for the kids!
The best biscuits I've ever tasted. Tender inside and crispy (almost crunchy) top and bottom. Make wonderful strawberry shortcakes. Try these. You will not be disappointed. I made them with low fat sour cream and they were just as good as with the full fat. I did slightly more than double the cinnamon but would leave as written to use with a meal. Very light cinnamon taste.
These are good!! The biscuit is tender and light. They have just a hint of cinnamon and they do go well with apple butter, thanks!!


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BWS2 013 - Advance of the Therian Formes! Unova Greatest Crisis!!
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October 5th, 2012 (5:26 AM).
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This episode was absolutely EPIC!
Best Wishes totally adds suspense, that was missing, to Pokémon anime!
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Exclusive SE SoCal Roadtrip Video!
Updated: March 25, 2008, 3:35 PM ET
With it snowing on the east coast, SE recently flew out a couple east coast team riders, Pat Laughlin and Chris Gerber to join them on a team trip down to San Diego. They met up with other west coast riders, Todd Lyons (SE TM) and Fernando Sabat. Justin Kosman was on hand to capture this footage of all the spots they hit, enjoy!
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New try 4/5/16. Had the Nash Vegas with pimento cheese and it was great. But even better was the Talliwacker. Ready to sit on the patio, soak up the sun and enjoy one or more of these with a good burger!
TL;DR: Service is spotty, food is mediocre, though they have a great booze selection and are very kind to drunks.
Like others, I was wondering what they were building for all those months in front of Frugal MacDoogal's. I'm also wondering why more businesses don't put up some kind of "coming soon" sign while they are being built. Before I get too far along, I want to explain my rating. I was torn between 3 and 4 stars. Since they are new (and hopefully improving), I went with a 4, but my rating might have also been inspired a little by the round of Woodford Reserve Four Wood bourbon my friend bought us!
A couple of guys in our group do enjoy their bourbons and they were the main reason we ended up here. When we are out, they will order typically want something fancy like Blanton's while I'm happy with Jim Beam or a beer. Everyone in our group likes burgers though, and we agree that the food was good, not the best ever but not bad. My cheeseburger was big and cooked right and the sweet potato fries were tasty.
The environment is very nice and the beer and spirits selections are impressive. Didn't take long to get service once we seated ourselves, but we were so loud it was probably hard to ignore us. Prices are reasonable and we think the potential there, especially once the weather is good enough to take advantage of the outdoor seating.
I've wandered in twice minutes before closing after ragers at the breweries down the road, and they've been kind enough to let me buy their last plates of the night and get me a cab. Super nice of them, and I won't begrudge them my money for it!
Stepped in for a few, but stayed for awhile. Cool spot to for date night. Just a bit dark and the TVs could be larger. The food smelled great, I had already eaten but I live close and will be back!
coolest bar i've been to in a while original, excellent drinks would have been 5 stars but only thing i ate was 1 oyster and it was bad
The Saucer is one of the best places to enjoy microbrews in a town with increasing choices. Service can be uneven and the food is unexceptional, but the staff trains regularly on the vast array of beer selections and the bartenders in particular are knowledgeable. If you are over twenty five you might prefer the vibe at happy hour and during weekend days as the place can become inundated with Vandy students on late evenings. Special events include beer tastings, a trivia night and live music from consistently average retro and alternative bands.
While they did "clean up" the Gold Rush, they also cleaned out much of the essence that made it the greatest bar in Nashville. It could use a bit more warmth...too many tall tables and stools were put in during renovation. Having a few boothes in the front room would help the atmosphere greatly. It has to potential to be great once again, but as it stands I visit out of nostalgia and because it was my home away from home for many years. This bar could really be great again, I still give it a decent rating out of loyalty, but they should try to cater to their old clientele if they want to become truly successful again.
The saucer offers a very knowledgeable staff. They can tell you what beer you will probably like, even if you aren't much of a beer drinker. It is very relaxed and has lots of comfortable seating. The beer garden is a great place to hang out, especially when the garage doors are open.
My first time at the Patterson was a huge success. After having dinner somewhere else stopped by to have a couple of cocktails and relax. I will say the Patterson has brought drink mixology to another level. Drink flavors that included rye bread and lime and ginger and mint. There was a party going on inside my mouth. Also, had the light dessert beignets with cinammon, sugar and salt. Wow, what a dessert. The ladies from Atlanta sitting beside me were yelling about having orgasms and that it was the best thing they had ever put in their mouth. What more can I say. I will definitely be back. I forgot to mention a really cool laid back atmosphere. This place has it all going on.
Rating Detail:
Food: 4
Service: 4
Atmosphere: 4
Value: 3
Overall: 4
Very friendly service and great music all the time. Wonderful, intimate-yet-funky atmosphere. Eclectic crowd - definitely a favorite!
Rating Detail:
Food: 5
Service: 5
Atmosphere: 5
Value: 4
Overall: 4


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Just wondering bc mine is toothless! Lol
Anyone else's LO not have teeth?
Posted 08/17/2012
None yet
Allie 10/19/05 Gold ( . ) ( . )!!! & Sean 12/17/11 Gold ( . ) ( . ) and going!!!. My two loves:)
Posted 08/17/2012
My kids never get teeth till 11-13 months.
Emily- Mom of 6 (11, 5, 4, 3, 2, 8mos)
Somnio Newborn and Child Photography
Posted 08/17/2012
will be 8 months on the 21 first and just saw one broke through today. its sharp. lol and i saw another white cap so that will be 2.
Posted 08/17/2012
7 months and 3 weeks and NO TEETH! Lol! But he is fierce with his gums! Lol!
Posted 08/17/2012
No teeth here either and no signs of teething but I'm not worried my oldest didn't get her first tooth until she was 9 mos
My husbands karma has given us another GIRL
Follow me on Instagram @mycookiesncakes
Posted 08/17/2012
Lo first one just poked through today. 7 months & 3 weeks
Me and DH '95
ODS'98, MDS'00, YDS'03, Christmas blessing '11, Little Turkey '15
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text: Babies Scared of Farts: Their Response is Hilarious. These adorable babies react in the most adorable/hilarious way to the sound of farts. This will make you laugh so hard! ClickLike Share This Story On Facebook Share on Facebook Share Next Story Get more stories like this delivered to your inbox! Leave a Reply Previous PostNext Post


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1200 Post Oak Blvd., Houston, TX 77056
- $2,603
- 183 Days on site
- Beds: 2
- Baths: 2 Full
- Apartment
SMS/Text REALLYO 54245 to 41411 to receive full contact and listing details direct to your phone. Apt#4176A - Houston, TX, 77056 1 bedroom $1,802-4,529 /mo 839-1,303 sf 2 bedroom $2,603-4,476 /mo 1,313-1,827 sf 3 bedroom $12,703-13,572 /mo 3,463-3,574 sf Deposit: 300+ Pet Policy: Cats:Yes Dogs:Yes Built: 2003 Location: Galleria Prices & Specials change daily, contact me for availability Features: Experience the Carefree Lifestyle of a Pedestrian, Highrise & Penthouse Apartments offer skyline views, Uptown Location - Best in City for Shopping and Dining!, 10' Coffered Ceilings, Crown Molding, Accent Walls, Hardwood & Slate Floors, Private Terrace, Garden Tubs, Gourmet Kitchens with New Quartz Countertops & more, 2 Resort-Style Pools with Sundecks, 24Hr Fitness Center, Fitness Classes, Social Events, Poker Room, Coffee bar, Private Wine Room & Chef Kitchen w/Entertaining Space, Complimentary Valet Service and 24 Hour Concierge, Brand New Dog Park with Wash Station! Community Amenities: 2 Pools, Assigned parking, BBQ grills, Elevators, Fitness center, Perimeter fence, Business center, Gated entrance, Community parking garage, Private detached garages($140/mo), Club house, Dry cleaning service Unit Amenities: Walk-in showers, Private patios/balconies, Frost free refrigerators, Attached garages, Custom carpet, W/D machines, Garden/large tubs, Microwaves, Self cleaning ovens, Garbage disposals, Non-carpeted flooring, Hi-speed internet, Cable ready, Walk-in closets, Ice makers, High ceilings, Dishwashers, Ceiling fans, Crown molding, Custom built-ins For more information about this community contact: Asad Shaikh (Agent) The Virtual Realty Group 214/997-6099 Refer to Apt#4176A powered by Apartment Data Services, LLC s37490 a4176A ad2361 i Copyright 2015 Apartment Data Services, LLC All Rights Reserved Equal Housing Opportunity d [ Syndicated via Reallyo. com 3-May-16. ID RLYO54245. Report listing at reallyo. com/report?listing=54245 ] Click here to learn more about this listing.
- Year Built: n/a
- 183 Days on site
- Apartment
- Beds: 2
- Baths: 2 Full
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Nearby Elementary Schools
- St Michael Catholic School
- 1833 Sage Rd
- The Fay School
- 105 N Post Oak Ln
- River Oaks Baptist School
- 2300 Willowick Rd
Nearby Middle Schools
- St Michael Catholic School
- 1833 Sage Rd
- Grady Middle
- 5215 San Felipe St
- River Oaks Baptist School
- 2300 Willowick Rd
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- T H Rogers School
- 5840 San Felipe St
- Soar Ctr
- 3233 Weslayan St
- Crossroads School
- 5822 Dolores St
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