Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains.

Kiu R, Shaw AG, Sim K, Acuna-Gonzalez A, Price CA, Bedwell H, Dreger SA, Fowler WJ, Cornwell E, Pickard D, Belteki G, Malsom J, Phillips S, Young GR, Schofield Z, Alcon-Giner C, Berrington JE, Stewart CJ, Dougan G, Clarke P, Douce G, Robinson SD, Kroll JS, Hall L. (2023)

Nature microbiology

Clostridium perfringens is an anaerobic toxin-producing bacterium associated with intestinal diseases, particularly in neonatal humans and animals. Infant gut microbiome studies have recently indicated a link between C. perfringens and the preterm infant disease necrotizing enterocolitis (NEC), with specific NEC cases associated with overabundant C. perfringens termed C. perfringens-associated NEC (CPA-NEC). In the present study, we carried out whole-genome sequencing of 272 C. perfringens isolates from 70 infants across 5 hospitals in the United Kingdom. In this retrospective analysis, we performed in-depth genomic analyses (virulence profiling, strain tracking and plasmid analysis) and experimentally characterized pathogenic traits of 31 strains, including 4 from CPA-NEC patients. We found that the gene encoding toxin perfringolysin O, pfoA, was largely deficient in a human-derived hypovirulent lineage, as well as certain colonization factors, in contrast to typical pfoA-encoding virulent lineages. We determined that infant-associated pfoA+ strains caused significantly more cellular damage than pfoA- strains in vitro, and further confirmed this virulence trait in vivo using an oral-challenge C57BL/6 murine model. These findings suggest both the importance of pfoA+ C. perfringens as a gut pathogen in preterm infants and areas for further investigation, including potential intervention and therapeutic strategies.

Nature microbiology

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