Cited by 349Clostridium difficile and Clostridium perfringens researchGut microbiota and healthInfection Control in Healthcare

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Antibiotic Treatment of Clostridium difficile Carrier Mice Triggers a Supershedder State, Spore-Mediated Transmission, and Severe Disease in Immunocompromised Hosts

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Lawley, Trevor D., Clare, Simon, Walker, Alan W., Goulding, David, Stabler, Richard A., Croucher, Nicholas, Mastroeni, Piero, Scott, Paul, Raisen, Claire, Mottram, Lynda, Fairweather, Neil F., Wren, Brendan W., Parkhill, Julian, Dougan, Gordon·2009·Infection and Immunity

DOI 10.1128/iai.00558-09PMC PMC2737984

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Abstract

Clostridium difficile persists in hospitals by exploiting an infection cycle that is dependent on humans shedding highly resistant and infectious spores. Here we show that human virulent C. difficile can asymptomatically colonize the intestines of immunocompetent mice, establishing a carrier state that persists for many months. C. difficile carrier mice consistently shed low levels of spores but, surprisingly, do not transmit infection to cohabiting mice. However, antibiotic treatment of carriers triggers a highly contagious supershedder state, characterized by a dramatic reduction in the intestinal microbiota species diversity, C. difficile overgrowth, and excretion of high levels of spores. Stopping antibiotic treatment normally leads to recovery of the intestinal microbiota species diversity and suppresses C. difficile levels, although some mice persist in the supershedding state for extended periods. Spore-mediated transmission to immunocompetent mice treated with antibiotics results in self-limiting mucosal inflammation of the large intestine. In contrast, transmission to mice whose innate immune responses are compromised (Myd88 −/− ) leads to a severe intestinal disease that is often fatal. Thus, mice can be used to investigate distinct stages of the C. difficile infection cycle and can serve as a valuable surrogate for studying the spore-mediated transmission and interactions between C. difficile and the host and its microbiota, and the results obtained should guide infection control measures.

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Authors: Lawley, T. D., Clare, S., Walker, A. W., Goulding, D., Stabler, R. A., Croucher, N., Mastroeni, P., Scott, P., Raisen, C., Mottram, L., Fairweather, N. F., Wren, B. W., Parkhill, J., & Dougan, G.
Affiliations: Microbial Pathogenesis Laboratory
Wellcome Sanger Institute (GB)
University of London (GB)
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
Imperial College London (GB)
Corresponding author: Lawley, Trevor D.
ORCID: Lawley, Trevor D.
Clare, Simon
Walker, Alan W.
Goulding, David
Stabler, Richard A.
Croucher, Nicholas
Mottram, Lynda
Fairweather, Neil F.
Wren, Brendan W.
Parkhill, Julian
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 2009-09
Volume: 77
Issue: 9
Pages: 3661-3669
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.00558-09
PMC: PMC2737984
OpenAlex: W2125181303
Cited by: 349
References: 66
Citations by year: 2026: 5 · 2025: 12 · 2024: 15 · 2023: 16 · 2022: 9 · 2021: 29 · 2020: 23 · 2019: 21 · 2018: 23 · 2017: 14 · 2016: 21 · 2015: 34 · 2014: 30 · 2013: 31 · 2012: 24
FWCI: 14.95
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Royal Society
Engineering and Physical Sciences Research Council (EP/E500412/1)
Topics: Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Infectious Diseases › Infection Control in Healthcare
Keywords: Clostridium difficile, asymptomatic carriage, antibiotic therapy, gut microbiota, MyD88 knockout mice, innate immunity, mucosal inflammation, infection cycle, infection control, mouse model
MeSH terms: Animals, Anti-Bacterial Agents, Carrier State, Enterocolitis, Pseudomembranous, Female, Intestines, Mice, Inbred C57BL, Spores, Bacterial, Clostridioides difficile, Immunocompromised Host, Mice, Myeloid Differentiation Factor 88

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Antibiotic Treatment of Clostridium difficile Carrier Mice Triggers a Supershedder State, Spore-Mediated Transmission, and Severe Disease in Immunocompromised Hosts

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