CDI

Genetic and phenotipic characterization of emerging hypervirulent Clostridium difficile: role and regulation of virulence factors

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 Obiettivo del progetto (Objective)

'Clostridium difficile is a Gram-positive, spore-forming anaerobic bacillus that often resides in the gut of mammals and is the causative agent of the illness C. difficile infection (CDI). The hospital environment and patients undergoing antibiotic treatment provide a discrete ecosystem where C. difficile persists and select virulent clones thrive. CDI is the most frequent cause of infectious diarrhea in hospitals worldwide, causing in the last decade outbreaks of increased severity in Europe and North America. The continued rise of CDI worldwide has been accompanied by the rapid emergence and transcontinental spread of at least two highly virulent clones that are commonly referred to as 027 and A-B. The overall aim of this project is to determine the genetic and phenotypic attributes that might explain the emergence of these hypervirulent 027 strains. To this end we will obtain mutants in genes we suspect to be important for 027 strains virulence. Those mutants will be characterized in detail by genetic and phenotypical studies. This project provides a unique opportunity to study the recent emergence of virulence and will contribute more generally to our understanding of how bacterial pathogens evolve.'

Introduzione (Teaser)

Higher incidence of Clostridium difficile infections (CDIs) is usually seen in hospitalised patients undergoing antibiotic treatment. Identifying the genetic and phenotypic attributes of such hyper-virulent bacterial strains may help explain why they emerge, and offer solutions for their eradication.

Descrizione progetto (Article)

Clostridium difficile causes infectious diarrhoea. Severe CDI outbreaks have been reported over the past decade as hospitals seem to facilitate the selection and spread of virulent forms of C. difficile.

Scientists on the EU-funded CDI project set out to investigate various aspects of Clostridium strains and their adaptation processes. To differentiate between hyper-virulent and epidemic strains, they mapped genetic differences to find genes implicated in bacterial virulence.

Hyper-virulent strains possess a different glycosylation pattern on their flagella, a lash-like structure used by bacteria for locomotion. Characterisation of the genes responsible for this novelty could unveil important bacterial targets that could also be exploited for therapeutic interventions.

Interestingly, epidemiologic studies showed that C. difficile is continuing to evolve in concert with human activity. Means to control bacterial spread and transmission are rather inefficient possibly due to antimicrobial resistance. Scientists tested the effect of various disinfectants on strains having different degrees of virulence to elucidate the mechanism of CDI. Only one oxidising agent was efficient at eradicating all bacterial strains, indicating that care should be taken when choosing antimicrobial agents against C. difficile.

Another potential explanation for the persistence of C. difficile is the formation of biofilm bacterial communities on various hospital surfaces or devices. Project members identified a spore-forming protein with a key role in biofilm formation that could also serve as a future drug target.

Overall, the CDI study provided significant knowledge on key attributes of C. difficile hyper-virulent strains and underscored the importance of investigating the causes behind their emergence. The identified molecules could prove useful in effective drug design for potent anti-bacterial action even against resistant strains.