Antibiotic resistance has devastating socioeconomic impacts globally. A plethora of alternatives to antibiotics are under investigation. Moreover, antimicrobial strategies that are less likely to develop resistance are immediately required to treat severe antibiotic-resistant infections.
Recently, a team of researchers led by Joseph M. Salvino & Farokh Dotiwala (The Wistar Institute, Philadelphia, PA, USA) discovered a new class of antibiotic which possesses dual mechanism of action and they named them as dual-acting immuno-antibiotics (DAIAs). This class of antibiotics kills bacteria and also simultaneously elevates the human immune system by cytotoxic γδ T cells. As the action is carried out at two different fronts, bacteria can hardly develop resistance against these compounds. Researchers screened inhibitors against IspH, an enzyme that is involved in the isoprenoid synthesis pathway, and modified them to redefine their potency at a molecular level. The isoprenoids synthesis pathway is important for the bacteria, however, it is absent in humans. Hence, inhibitors targeting the IspH enzyme did not show any evidence of side effects in the mouse model. Researchers have demonstrated the activity of their compound against several multidrug-resistant bacteria such as Pseudomonas Enterobacter, Acinetobacter, Mycobacterium, Vibrio, Klebsiella, Shigella, Yersinia, and Bacillus and Salmonella.
To recapitulate, the aforementioned discovery has opened up new avenues for the development of antimicrobial strategies that are effective against antibiotic-resistant infections due to their dual mechanism of action.
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Upinzani wa viuavijasumu una athari mbaya za kijamii na kiuchumi ulimwenguni pote. Njia nyingi za badala za viuavijasumu zinachunguzwa. Kwa kuongezea, mikakati ya kupambana na viini visivyo na uwezekano wa kuendeleza upinzani inahitajika mara moja kutibu maambukizo mazito ya kukinza viuavijasumu. "Timu ya watafiti iliyoongozwa na Joseph M. Salvino na Farooq Duttwala (Wistar Institute, Philadelphia, PA, USA) imegundua aina mpya ya dawa za kuua viini ambazo zina ""mfumo wa vitendo viwili"" na kuziita ""dawa za kuua viini za vitendo viwili.""" Darasa hili la viuavijasumu huua bakteria na pia kwa wakati mmoja huinua mfumo wa kinga ya binadamu kwa chembe za cytotoxic γδ T. Kwa kuwa hatua hiyo hufanywa katika sehemu mbili tofauti, ni vigumu kwa bakteria kusitawisha upinzani dhidi ya kemikali hizo. Watafiti walichunguza inhibitors dhidi ya IsH1N1, enzyme inayohusika katika njia ya synthesis ya isoprenoid, na kuibadilisha ili kuelezea nguvu zao katika kiwango cha molekuli. Njia ya utengenezaji wa isoprenoids ni muhimu kwa bakteria, hata hivyo, haipo kwa wanadamu. Kwa hiyo, inhibitors kulenga enzyme IspH hakuonyesha ushahidi wowote wa athari za upande katika mfano panya. Utafiti huo ulionyesha kuwa kemikali hiyo inaweza kuua bakteria nyingi zinazopinga dawa kama vile Pseudomonas enterobacter, Acinetobacter, Mycobacterium, Vibrio, Klebsiella, Shigella, Yersinia, Bacillus na Salmonella. Kwa muhtasari, uvumbuzi huo umefungua njia mpya za maendeleo ya mikakati ya antimicrobial ambayo ni ufanisi dhidi ya maambukizo ya antibiotic-resistant kutokana na utaratibu wao wa hatua mbili. Ili kusoma zaidi kuhusu makala hiyo, tembelea: (LINK)