The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Antibiotic Treatment of Clostridium difficile Carrier Mice Triggers a Supershedder State, Spore-Mediated Transmission, and Severe Disease in Immunocompromised Hosts
Open accessAbstract
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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“In both a human-associated microbiota43-45 and macroecological46,47 context, higher phylogenetic diversity is associated with greater ecosystem resilience and productivity.”
From Sequencing ancient calcified dental plaque shows changes in oral microbiota with dietary shifts of the Neolithic and Industrial revolutions (2013) · cites this paper as [44]
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Metadata
- 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
- 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
- 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
- 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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