Characterizing the interactions between attaching and effacing pathogens and the gastrointestinal microbiota
Diarrheal illnesses remain a major cause of sickness and death worldwide, killing approximately 760,000 children under the age of five each year. This project seeks to better understand one major cause: bacteria known as attaching and effacing (A/E) pathogens. This group includes several classes of pathogens: i) a class that causes death primarily among children in developing countries, and ii) a class with potentially life-threatening complications such as kidney failure in both developing and developed countries.
First, the normal community of microbes inhabiting the healthy mammalian digestive tract (the gut microbiota) represents a major challenge for A/E pathogens by competing for nutrients and possibly by producing molecules that inhibit the A/E pathogens. We will investigate how A/E pathogens sense and adapt to the presence of the gut microbiota with a view to gaining insights into their overall infection strategy.
Second, we will seek out species within the gut microbiota that inhibit A/E pathogens. Chemicals that they produce could form the basis of drug discovery programs for novel antibiotics.
Our final objective is to characterize one genetic system that A/E pathogens use to sense their surroundings: the Cpx envelope stress response. This system triggers production of damage-repair proteins when it senses damage to the envelope of the bacterial cell. We will study whether and how these repair proteins are required for A/E pathogens to infect mice. If so, they represent a potential target for developing novel antibiotics.
This project will yield a better understanding of a major cause of illness and death and might give rise to new avenues of research for novel antibiotics to counter it.