1. Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains
- Author
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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 Clarke, Gillian Douce, Stephen D. Robinson, J. Simon Kroll, Lindsay J. Hall, Kiu, Raymond [0000-0002-4483-1215], Acuna-Gonzalez, Antia [0000-0002-8062-925X], Price, Christopher A [0000-0003-3161-1704], Dreger, Sally A [0000-0001-7104-6776], Young, Gregory R [0000-0001-5342-1421], Stewart, Christopher J [0000-0002-6033-338X], Clarke, Paul [0000-0001-6203-7632], Douce, Gillian [0000-0002-6654-7346], Robinson, Stephen D [0000-0002-6606-7588], Hall, Lindsay J [0000-0001-8938-5709], and Apollo - University of Cambridge Repository
- Subjects
Microbiology (medical) ,Virulence ,Clostridium perfringens ,Immunology ,Infant, Newborn ,Infant ,Cell Biology ,Genomics ,Applied Microbiology and Biotechnology ,Microbiology ,Infant, Newborn, Diseases ,Mice ,Genetics ,Humans ,Animals ,Infant, Premature ,Retrospective Studies - 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.
- Published
- 2023