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

Raymond Kiu, Alexander G. Shaw, Kathleen Sim, Antia Acuna-Gonzalez, Christopher A. Price, Harley Bedwell, Sally A. Dreger, Wesley J. Fowler, Emma Cornwell, Derek Pickard, Gusztav Belteki, Jennifer Malsom, Sarah Phillips, Gregory R. Young, Zoe Schofield, Cristina Alcon-Giner, Janet E. Berrington, Christopher J. Stewart, Gordon Dougan, Paul ClarkeGillian Douce, Stephen D. Robinson, J. Simon Kroll, Lindsay J. Hall

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Abstract

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.

Original languageEnglish
Pages (from-to)1160-1175
Number of pages16
JournalNature Microbiology
Volume8
Issue number6
DOIs
Publication statusPublished - 25 May 2023

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