title: Toxin-positiveClostridium difficilelatently infect mouse colonies and protect against highly pathogenicC. difficile.
abstract: Clostridium difficileis a toxin-producing bacterium and a leading cause of antibiotic-associated disease. The ability ofC. difficileto form spores and infect antibiotic-treated persons at low multiplicity of infection (MOI) underlies its large disease burden. However,C. difficile-induced disease might also result from long-harbouredC. difficilethat blooms in individuals administered antibiotics.
  
  
  
  Mice purchased from multiple vendors and repeatedly testing negative for this pathogen by quantitative PCR bloomedC. difficilefollowing antibiotic treatment. This endogenousC. difficilestrain, herein termed LEM1, which formed spores and produced toxin, was compared with highly pathogenicC. difficilestrain VPI10463.
  
  
  
  Whole-genome sequencing revealed that LEM1 and VPI10463 shared 95% of their genes, including all known virulence genes. In contrast to VPI10463, LEM1 did not induce overt disease when administered to antibiotic-treated or germ-free mice, even at high doses. Rather, blooms of LEM1 correlated with survival following VPI10463 inoculation, and exogenous administration of LEM1 before or shortly following VPI10463 inoculation preventedC. difficile-induced death. Accordingly, despite similar growth properties in vitro, LEM1 strongly outcompeted VPI10463 in mice even at 100-fold lower inocula.
  
  
  
  These results highlight the difficulty of determining whether individual cases ofC. difficileinfection resulted from a bloom of endogenousC. difficileor a new exposure to this pathogen. In addition to impacting the design of studies using mouse models ofC. difficile-induced disease, this study identified, isolated and characterised an endogenous murine spore-formingC. difficilestrain able to decrease colonisation, associated disease and death induced by a pathogenicC. difficilestrain.
authors.affiliation: Center for Inflammation Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Lucie
authors.initials: L
authors.lastname: Etienne-Mesmin
authors.affiliation: Center for Inflammation Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: Chassaing
authors.affiliation: Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, Georgia, USA.
authors.forename: Oluwaseyi
authors.initials: O
authors.lastname: Adekunle
authors.affiliation: PennCHOP Microbiome, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mattei
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Frederic D
authors.identifier: 0000-0003-4740-4056
authors.initials: FD
authors.lastname: Bushman
authors.affiliation: Center for Inflammation Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gewirtz
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins; D016360:Clostridioides difficile / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D003015:Clostridium Infections / Q000382:microbiology*; D007422:Intestines / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014774:Virulence; D000073336:Whole Genome Sequencing
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins
keywords: ANTIBIOTICS; BACTERIAL INFECTION; COLONIC MICROFLORA; INFECTIOUS DISEASE; INTESTINAL BACTERIA