Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification Academic Article Article uri icon

Overview

MeSH Major

  • Aging
  • Fibroblast Growth Factor 7
  • Gonadal Steroid Hormones
  • Interleukin-7
  • Thymus Gland

abstract

  • © 2018 Sorbara et al. 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.

publication date

  • January 7, 2019

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1084/jem.20181639

PubMed ID

  • 30563917

Additional Document Info

start page

  • 84

end page

  • 98

volume

  • 216

number

  • 1