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

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Shaw, Alexander G 
Sim, Kathleen 
Acuna-Gonzalez, Antia  ORCID logo
Price, Christopher A  ORCID logo


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.



Infant, Infant, Newborn, Humans, Animals, Mice, Clostridium perfringens, Infant, Premature, Retrospective Studies, Virulence, Genomics, Infant, Newborn, Diseases

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Nat Microbiol

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Springer Science and Business Media LLC
Wellcome Trust (Wellcome) (100974/C/13/Z, 220876/Z/20/Z)
RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) (BB/R012490/1, BBS/E/F/000PR10353, BBS/E/F/00PR10356)