Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification Journal Article


Authors: Sorbara, M. T.; Dubin, K.; Littmann, E. R.; Moody, T. U.; Fontana, E.; Seok, R.; Leiner, I. M.; Taur, Y.; Peled, J. U.; van den Brink, M. R. M.; Litvak, Y.; Bäumler, A. J.; Chaubard, J. L.; Pickard, A. J.; Cross, J. R.; Pamer, E. G.
Article Title: Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification
Abstract: Klebsiella pneumoniae, Escherichia coli, 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 Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis 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 O2 and NO3 respiration confer upon Enterobacteriaceae during expansion. Reestablishment of a microbiota that produces SCFAs enhances clearance of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis from the intestinal lumen and represents a potential therapeutic approach to enhance clearance of antibiotic-resistant pathogens. © 2018 Sorbara et al.
Journal Title: Journal of Experimental Medicine
Volume: 216
Issue: 1
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 2019-01-07
Start Page: 84
End Page: 98
Language: English
DOI: 10.1084/jem.20181639
PUBMED: 30563917
PROVIDER: scopus
PMCID: PMC6314524
DOI/URL:
Notes: Article -- Export Date: 1 February 2019 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Eric Pamer
    237 Pamer
  2. Ingrid Leiner
    44 Leiner
  3. Justin Robert Cross
    46 Cross
  4. Ying Taur
    81 Taur
  5. Krista Dubin
    4 Dubin
  6. Jonathan U Peled
    35 Peled
  7. Thomas Ulysses Moody
    1 Moody
  8. Ruth Seok
    1 Seok