Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae.
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.
Immunology Program and Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, New York, United States of America.
Silvia
S
Caballero
Immunology Program and Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Rebecca
R
Carter
Molecular Cytology Core Facility, Sloan-Kettering Institute, New York, New York, United States of America.
Xu
X
Ke
Immunology Program and Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Bože
B
Sušac
Immunology Program and Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Ingrid M
IM
Leiner
Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Grace J
GJ
Kim
Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Liza
L
Miller
Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Lilan
L
Ling
Molecular Cytology Core Facility, Sloan-Kettering Institute, New York, New York, United States of America.
Katia
K
Manova
Immunology Program and Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, New York, United States of America; Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Eric G
EG
Pamer
D000667:Ampicillin / Q000009:adverse effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology; D015780:Carbapenems / Q000494:pharmacology; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial; D004751:Enteritis / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control; D016984:Enterococcus faecium / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D000069467:Fecal Microbiota Transplantation; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control; D054884:Host-Pathogen Interactions; D017404:In Situ Hybridization, Fluorescence; D007413:Intestinal Mucosa / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology; D007710:Klebsiella Infections / Q000382:microbiology* / Q000473:pathology / Q000517:prevention & control; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D008810:Mice, Inbred C57BL; D056265:Microbial Interactions; D013047:Specific Pathogen-Free Organisms; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000667:Ampicillin