2021 New Investigator Grant
Tera Levin, Ph.D. Assistant Professor, Department of Biological Sciences, University of Pittsburgh
Playing with fire: How bacteria deploy self-targeting antimicrobials during inter-bacterial battles
In natural environments, competition between bacterial species can be fierce, with bacteria secreting diverse arrays of toxin proteins, antibiotics or other toxic small molecules to antagonize their neighbors. Because many pathogenic bacteria cycle between human infection and the environment, the ability to succeed during microbe-on-microbe competition is a necessary prerequisite for these organisms to jump to humans and cause disease. Here, we study mechanisms of interbacterial competition in the bacterium Legionella pneumophila, which can colonize building plumbing systems and thereby cause outbreaks of a deadly pneumonia-like disease called Legionnaires’ disease. We previously discovered the first known antimicrobial produced by L. pneumophila, called homogentisic acid (HGA), which may be used during building colonization. Curiously, L. pneumophila that produce HGA are not wholly immune to its effects, making it a mystery how these bacteria can use potentially self-targeting antimicrobials during inter-bacterial battles. We found HGA susceptibility is linked to cell density: low-density bacteria are strongly inhibited by HGA whereas high-density cells are protected. This proposal will investigate this unusual density-dependence of L. pneumophila susceptibility to HGA, and figure out how high-density resistance works. This project will reveal how L. pneumophila successfully competes with benign bacteria to colonize aquatic niches, while avoiding collateral damage to its own cells. In the process, it may point to new strategies to control Legionella colonization and prevent these deadly disease outbreaks.