Open AccessAntibiotic Treatment of Clostridium difficile Carrier Mice Triggers a Supershedder State, Spore-Mediated Transmission, and Severe Disease in Immunocompromised Hosts
Author(s) -
Trevor D. Lawley,
Simon Clare,
Alan W. Walker,
David Goulding,
Richard A. Stabler,
Nicholas J. Croucher,
Pietro Mastroeni,
Paul D. Scott,
Claire Raisen,
Lynda Mottram,
Neil F. Fairweather,
Brendan W. Wren,
Julian Parkhill,
Gordon Dougan
Publication year - 2009
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00558-09
Subject(s) - clostridium difficile , biology , microbiology and biotechnology , antibiotics , transmission (telecommunications) , gut flora , virulence , immunology , immune system , innate immune system , immunity , dysbiosis , biochemistry , electrical engineering , gene , engineering
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 virulentC. 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 suppressesC. 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 theC. difficile infection cycle and can serve as a valuable surrogate for studying the spore-mediated transmission and interactions betweenC. difficile and the host and its microbiota, and the results obtained should guide infection control measures.