The gut microbiota consists of a complex microbial community that plays a number of important roles in human health, including protection from invading intestinal pathogens. Extracellular electron transfer (EET) describes a respiratory strategy that allows microbes to grow using electron acceptors exterior to the cell. I recently discovered a distinctive flavin-based extracellular electron transfer (FLEET) mechanism that is prevalent in gram-positive members of the gut microbiota, as well as the intestinal pathogens Listeria monocytogenes and multidrug-resistant Enterococcus faecalis. Traditionally viewed as a highly specialized growth strategy, the discovery of FLEET extends the relevance of EET into novel nutrient-rich environments, including within the complex microbial communities that define the gut microbiota. The studies proposed here seek to address: 1) the molecular basis of FLEET function, 2) determine the role of FLEET and associated respiratory mechanisms in the outgrowth of gram-positive pathogens in the gut, and 3) assess the effect of transferring high-energy electrons into the surrounding environment on gut microbial communities. Findings from these experiments promise to shape our understanding of interactions within microbial communities and metabolic strategies employed by gram-positive pathogens for intestinal outgrowth.

Public Health Relevance

Extracellular electron transfer (EET) describes a microbial growth strategy that results in high energy electrons being relocated from the cytosol to the surrounding environment. Following up on the recent discovery that a flavin-based EET mechanism is common in both members of the human gut microbiota and enteric microbial pathogens, the studies proposed here seek to address mechanisms by which EET shapes microbial communities and contributes to bacterial pathogenesis. The resulting findings could have applications for the probiotic formulations and the treatment of microbial infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Career Transition Award (K22)
Project #
5K22AI144031-02
Application #
10114194
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Baqar, Shahida
Project Start
2020-02-26
Project End
2022-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637