Acuna-Gonzalez A

Alcon-Giner C

Bedwell H

Belteki G

Berrington JE

Clarke P

Cornwell E

Douce G

Dougan G

Dreger SA

Fowler WJ

Hall LJ

Kiu R

Kroll JS

Malsom J

Phillips S

Pickard D

Price CA

Robinson SD

Schofield Z

Shaw AG

Sim K

Stewart CJ

Young GR

\ua9 2023, The Author(s).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

Newcastle University E-Prints

English

Particular genomic and virulence traits associated with preterm infant-derived toxigenic <em>Clostridium perfringens</em> strains

Particular genomic and virulence traits associated with preterm infant-derived toxigenic <em>Clostridium perfringens</em> strains

Abstract

Similar works

Full text

Available Versions

Newcastle University E-Prints