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

Published version
Peer-reviewed

Repository DOI


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Authors

Shaw, Alexander G 
Sim, Kathleen 
Acuna-Gonzalez, Antia  ORCID logo  https://orcid.org/0000-0002-8062-925X
Price, Christopher A  ORCID logo  https://orcid.org/0000-0003-3161-1704

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.

Description

Keywords

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

Journal Title

Nat Microbiol

Conference Name

Journal ISSN

2058-5276
2058-5276

Volume Title

8

Publisher

Springer Science and Business Media LLC
Sponsorship
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)