Title | Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Sorbara MT, Dubin K, Littmann ER, Moody TU, Fontana E, Seok R, Leiner IM, Taur Y, Peled JU, van den Brink MRM, Litvak Y, Bäumler AJ, Chaubard J-L, Pickard AJ, Cross JR, Pamer EG |
Journal | J Exp Med |
Volume | 216 |
Issue | 1 |
Pagination | 84-98 |
Date Published | 2019 01 07 |
ISSN | 1540-9538 |
Keywords | Animals, Colon, Drug Resistance, Bacterial, Enterobacteriaceae, Enterobacteriaceae Infections, Fatty Acids, Female, Gastrointestinal Microbiome, Humans, Hydrogen-Ion Concentration, Male, Mice |
Abstract | , , and other members of the Enterobacteriaceae family are common human pathogens that have acquired broad antibiotic resistance, rendering infection by some strains virtually untreatable. Enterobacteriaceae are intestinal residents, but generally represent <1% of the adult colonic microbiota. Antibiotic-mediated destruction of the microbiota enables Enterobacteriaceae to expand to high densities in the colon, markedly increasing the risk of bloodstream invasion, sepsis, and death. Here, we demonstrate that an antibiotic-naive microbiota suppresses growth of antibiotic-resistant clinical isolates of , , and by acidifying the proximal colon and triggering short chain fatty acid (SCFA)-mediated intracellular acidification. High concentrations of SCFAs and the acidic environment counter the competitive edge that O and NO respiration confer upon Enterobacteriaceae during expansion. Reestablishment of a microbiota that produces SCFAs enhances clearance of , , and from the intestinal lumen and represents a potential therapeutic approach to enhance clearance of antibiotic-resistant pathogens. |
DOI | 10.1084/jem.20181639 |
Alternate Journal | J. Exp. Med. |
PubMed ID | 30563917 |
PubMed Central ID | PMC6314524 |
Grant List | FRN 152527 / / CIHR / Canada R01 AI042135 / AI / NIAID NIH HHS / United States U01 AI124275 / AI / NIAID NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States |
Submitted by api_import on December 20, 2019 - 3:23pm