Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae

PLoS Pathog. 2015 Sep 3;11(9):e1005132. doi: 10.1371/journal.ppat.1005132. eCollection 2015 Sep.

Abstract

Antibiotic resistance among enterococci and γ-proteobacteria is an increasing problem in healthcare settings. Dense colonization of the gut by antibiotic-resistant bacteria facilitates their spread between patients and also leads to bloodstream and other systemic infections. Antibiotic-mediated destruction of the intestinal microbiota and consequent loss of colonization resistance are critical factors leading to persistence and spread of antibiotic-resistant bacteria. The mechanisms underlying microbiota-mediated colonization resistance remain incompletely defined and are likely distinct for different antibiotic-resistant bacterial species. It is unclear whether enterococci or γ-proteobacteria, upon expanding to high density in the gut, confer colonization resistance against competing bacterial species. Herein, we demonstrate that dense intestinal colonization with vancomycin-resistant Enterococcus faecium (VRE) does not reduce in vivo growth of carbapenem-resistant Klebsiella pneumoniae. Reciprocally, K. pneumoniae does not impair intestinal colonization by VRE. In contrast, transplantation of a diverse fecal microbiota eliminates both VRE and K. pneumoniae from the gut. Fluorescence in situ hybridization demonstrates that VRE and K. pneumoniae localize to the same regions in the colon but differ with respect to stimulation and invasion of the colonic mucus layer. While VRE and K. pneumoniae occupy the same three-dimensional space within the gut lumen, their independent growth and persistence in the gut suggests that they reside in distinct niches that satisfy their specific in vivo metabolic needs.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ampicillin / adverse effects
  • Animals
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacology
  • Carbapenems / pharmacology
  • Colony Count, Microbial
  • Drug Resistance, Bacterial
  • Enteritis / microbiology*
  • Enteritis / pathology
  • Enteritis / prevention & control
  • Enterococcus faecium / drug effects
  • Enterococcus faecium / growth & development
  • Enterococcus faecium / isolation & purification
  • Enterococcus faecium / physiology*
  • Fecal Microbiota Transplantation
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Gram-Positive Bacterial Infections / microbiology*
  • Gram-Positive Bacterial Infections / pathology
  • Gram-Positive Bacterial Infections / prevention & control
  • Host-Pathogen Interactions
  • In Situ Hybridization, Fluorescence
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Klebsiella Infections / microbiology*
  • Klebsiella Infections / pathology
  • Klebsiella Infections / prevention & control
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / growth & development
  • Klebsiella pneumoniae / isolation & purification
  • Klebsiella pneumoniae / physiology*
  • Mice, Inbred C57BL
  • Microbial Interactions
  • Specific Pathogen-Free Organisms
  • Vancomycin-Resistant Enterococci / drug effects
  • Vancomycin-Resistant Enterococci / growth & development
  • Vancomycin-Resistant Enterococci / isolation & purification
  • Vancomycin-Resistant Enterococci / physiology*

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Ampicillin