New trends in Clostridium difficile virulence and pathogenesis.
The disease spectrum caused by Clostridium difficile infection ranges from antibiotic-associated diarrhoea to life-threatening clinical manifestations such as pseudomembranous colitis. C. difficile infection is precipitated by antimicrobial therapy that causes a disruption of the normal colonic microbiota, predisposing to C. difficile intestinal colonisation. The pathogenicity of C. difficile is mediated by two exotoxins, TcdA and TcdB, both of which damage the human colonic mucosa and are potent cytotoxic enzymes. C. difficile must first be implanted in the gut and attach to epithelial cells, which are protected by a layer of dense mucus. Confirmed and putative accessory virulence factors that could play a role in adherence and intestinal colonisation have been identified and include proteolytic enzymes and adhesins. Recently, the epidemiology of C. difficile infection has radically changed and an increased incidence is associated with outbreaks in North America and Europe. Several reports suggest that disease severity is increasing to include sepsis syndrome and toxin megacolon. Elderly, debilitated patients in hospitals and nursing homes are particularly vulnerable. A hypervirulent, epidemic strain has been associated with the changing epidemiology and severity of disease. Here, we review the characteristics of the epidemic NAP1, PCR ribotype 027 C. difficile strain that could explain its hypervirulence and epidemic spread.
Denève
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EA 4043, Université Paris-Sud, Châtenay-Malabry, France.
Janoir
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Poilane
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Fantinato
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Collignon
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D018829:Adhesins, Bacterial / Q000096:biosynthesis; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000096:biosynthesis; D001427:Bacterial Toxins / Q000096:biosynthesis; D015373:Bacterial Typing Techniques; D016360:Clostridioides difficile / Q000145:classification* / Q000472:pathogenicity*; D004196:Disease Outbreaks; D004761:Enterocolitis, Pseudomembranous / Q000453:epidemiology* / Q000382:microbiology*; D004768:Enterotoxins / Q000096:biosynthesis; D005060:Europe / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D009656:North America / Q000453:epidemiology; D010447:Peptide Hydrolases / Q000096:biosynthesis; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis
D018829:Adhesins, Bacterial; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D037521:Virulence Factors; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D010447:Peptide Hydrolases