Abstract
Clostridium difficile is responsible for a wide spectrum of infection from asymptomatic carriage to severe, relapsing colitis. Since 2003, C. difficile infections have increased with a higher morbidity and mortality due to the emergence of epidemic and hypervirulent C. difficile strains such as those of the epidemic lineage 027/BI/NAP1. To decipher the hypervirulence and epidemicity of 027 strains, we analyzed gene expression profiles of the R20291 027 strain using a monoxenic mouse model during the first 38h of infection. A total of 741 genes were differentially expressed during the course of infection. They are mainly distributed in functional categories involved in host adaptation. Several genes of PTS and ABC transporters were significantly regulated during the infection, underlying the ability of strain R20291 to adapt its metabolism according to nutrient availability in the digestive tract. In this animal model, despite the early sporulation process, sporulation efficiency seems to indicate that growth of R20291 vegetative cells versus spores were favored during infection. The bacterial mechanisms associated to adaptability and flexibility within the gut environment, in addition to the virulence factor expression and antibiotic resistance, should contribute to the epidemicity and hypervirulence of the C. difficile 027 strains.
Highlights
Clostridium difficile is a Gram positive, spore forming, anaerobic bacterium and is the major cause of nosocomial intestinal disease associated with antibiotic therapy
The pathogenesis of C. difficile infection (CDI) begins by the disruption of the normal colonic microbiota by antibiotics allowing the germination of contaminating spores and the colonization of the gastrointestinal tract by vegetative forms [3]
As already observed with strain 630, genes of strain R20291 involved in metabolic functions, transport, stress response or coding for proteins with unknown functions, were the most regulated genes during the in vivo kinetic study
Summary
Clostridium difficile is a Gram positive, spore forming, anaerobic bacterium and is the major cause of nosocomial intestinal disease associated with antibiotic therapy. C. difficile infection (CDI) has reached an epidemic state with increasing incidence and severity both in healthcare and community settings. This rise in morbidity and mortality results from emergence of the C. difficile epidemic lineage 027/BI/NAP1, whose strains have spread throughout developed countries [1,2]. The last step corresponds to the production of the major virulence factors of C. difficile, the toxins TcdA and TcdB that modify the actin skeleton of the intestinal cells by glucosylation of the Rho proteins [13,14,15,16]. A third toxin, the binary toxin is produced by some strains such as the 027 strains, which possibly potentiates toxicity of TcdA and TcdB, and leads to more severe diseases [17]
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