How Bacteria Respond to Stress
Bacteria and the human immune system have a complex relationship. Abundant, nonharmful bacteria provide numerous benefits, but pathogenic bacteria impose a large burden of morbidity and mortality. The innate immune system therefore has sophisticated methods of combat, restricting the growth of invading bacteria by limiting access to essential nutrient metal ions (nutritional immunity) and by producing antimicrobial peptides and enzymes that attack the bacterial cell envelope. Potential pathogens respond to these threats by activating specific adaptive responses, many of which are critical for virulence.
Using Bacillus subtilis as a model system, John D. Helmann, Microbiology, is working to understand the mechanisms by which bacteria respond to specific stresses—to both metal ion limitation and excess, as well as antibiotics that interfere with the integrity of the cell envelope. The resulting insights are relevant for understanding the mechanisms that allow bacterial cells (both beneficial and harmful) to adapt to the host environment.
This work continues previous research by Helmann’s group, which identified transcription factors responsible for maintaining metal ion homeostasis in bacteria. The group is now characterizing the genes regulated by these transcription factors, their roles in metal homeostasis, and identifying the physiological effects that result from both metal ion limitation and intoxication.
In a second project, the group is investigating how cells respond to stresses that affect the cell envelope, a target for many of the most important antibiotics. One focus will be investigating mutations in the cell’s stress response pathways that reduce antibacterial resistance, which will shed light on antibiotic tolerance and resistance in pathogens. NIH Award Number: 1R35GM122461-01