PMID- 31907198 OWN - NLM STAT- MEDLINE DCOM- 20200708 LR - 20200924 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 88 IP - 4 DP - 2020 Mar 23 TI - Impact of Antibiotic-Resistant Bacteria on Immune Activation and Clostridioides difficile Infection in the Mouse Intestine. LID - 10.1128/IAI.00362-19 [doi] LID - e00362-19 AB - Antibiotic treatment of patients undergoing complex medical treatments can deplete commensal bacterial strains from the intestinal microbiota, thereby reducing colonization resistance against a wide range of antibiotic-resistant pathogens. Loss of colonization resistance can lead to marked expansion of vancomycin-resistant Enterococcus faecium (VRE), Klebsiella pneumoniae, and Escherichia coli in the intestinal lumen, predisposing patients to bloodstream invasion and sepsis. The impact of intestinal domination by these antibiotic-resistant pathogens on mucosal immune defenses and epithelial and mucin-mediated barrier integrity is unclear. We used a mouse model to study the impact of intestinal domination by antibiotic-resistant bacterial species and strains on the colonic mucosa. Intestinal colonization with K. pneumoniae, Proteus mirabilis, or Enterobacter cloacae promoted greater recruitment of neutrophils to the colonic mucosa. To test the hypothesis that the residual microbiota influences the severity of colitis caused by infection with Clostridioides difficile, we coinfected mice that were colonized with ampicillin-resistant bacteria with a virulent strain of C. difficile and monitored colonization and pathogenesis. Despite the compositional differences in the gut microbiota, the severity of C. difficile infection (CDI) and mortality did not differ significantly between mice colonized with different ampicillin-resistant bacterial species. Our results suggest that the virulence mechanisms enabling CDI and epithelial destruction outweigh the relatively minor impact of less-virulent antibiotic-resistant intestinal bacteria on the outcome of CDI. CI - Copyright (c) 2020 American Society for Microbiology. FAU - Keith, James W AU - Keith JW AD - Immunology Program, Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Dong, Qiwen AU - Dong Q AD - Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Sorbara, Matthew T AU - Sorbara MT AD - Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Becattini, Simone AU - Becattini S AD - Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Sia, Jonathan K AU - Sia JK AD - Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Gjonbalaj, Mergim AU - Gjonbalaj M AD - Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Seok, Ruth AU - Seok R AD - Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Leiner, Ingrid M AU - Leiner IM AD - Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Littmann, Eric R AU - Littmann ER AD - Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Pamer, Eric G AU - Pamer EG AD - Immunology Program, Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, New York, USA egpamer@uchicago.edu. AD - Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA. AD - Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, USA. AD - Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States GR - R01 AI042135/AI/NIAID NIH HHS/United States GR - R01 AI095706/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20200323 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Anti-Bacterial Agents) SB - IM MH - Animals MH - Anti-Bacterial Agents/*administration & dosage MH - Clostridium Infections/microbiology/*physiopathology MH - Colitis/microbiology/physiopathology MH - Disease Models, Animal MH - *Drug Resistance, Bacterial MH - Enterobacter cloacae/drug effects/*growth & development MH - Enterobacteriaceae Infections/*complications/drug therapy MH - Klebsiella pneumoniae/drug effects/*growth & development MH - Mice MH - Microbial Interactions MH - Proteus mirabilis/drug effects/*growth & development MH - Survival Analysis PMC - PMC7093144 OTO - NOTNLM OT - immunology EDAT- 2020/01/08 06:00 MHDA- 2020/07/09 06:00 PMCR- 2020/09/23 CRDT- 2020/01/08 06:00 PHST- 2019/05/08 00:00 [received] PHST- 2019/12/20 00:00 [accepted] PHST- 2020/01/08 06:00 [pubmed] PHST- 2020/07/09 06:00 [medline] PHST- 2020/01/08 06:00 [entrez] PHST- 2020/09/23 00:00 [pmc-release] AID - IAI.00362-19 [pii] AID - 00362-19 [pii] AID - 10.1128/IAI.00362-19 [doi] PST - epublish SO - Infect Immun. 2020 Mar 23;88(4):e00362-19. doi: 10.1128/IAI.00362-19. Print 2020 Mar 23.