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Lookup NU author(s): Chris Price, Professor Janet Berrington, Professor Christopher StewartORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 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.
Author(s): Kiu R, Shaw AG, Sim K, Acuna-Gonzalez A, Price CA, Bedwell H, Dreger SA, Fowler WJ, Cornwell E, Pickard D, Belteki G, Malsom J, Phillips S, Young GR, Schofield Z, Alcon-Giner C, Berrington JE, Stewart CJ, Dougan G, Clarke P, Douce G, Robinson SD, Kroll JS, Hall LJ
Publication type: Article
Publication status: Published
Journal: Nature Microbiology
Year: 2023
Volume: 8
Pages: 1160-1175
Print publication date: 01/06/2023
Online publication date: 25/05/2023
Acceptance date: 17/04/2023
Date deposited: 08/06/2023
ISSN (electronic): 2058-5276
Publisher: Nature Research
URL: https://doi.org/10.1038/s41564-023-01385-z
DOI: 10.1038/s41564-023-01385-z
Data Access Statement: Genome assemblies of 171 C. perfringens isolates were retrieved from the National Center for Biotechnology Information’s (NCBI) GenBank (downloaded on 2 April 2020), while 96 C. perfringens food-poisoning-associated, isolated genomes were downloaded (May 2022) from the European Nucleotide Archive under accession no. PRJEB25764 (Supplementary Table 3). Another 117 C. perfringens metagenome-assembled genomes and 17 C. perfringens isolated genomes were retrieved from the UHGG v.2.0 collection (May 2022; Supplementary Table 3). Sequencing raw reads and draft genome assemblies for 272 C. perfringens isolates generated in the present study are publicly available in the NCBI Sequence Read Archive (SRA) and GenBank respectively, under accession no. PRJNA755973 (Supplementary Table 3). The 16S rRNA gene amplicon sequence reads (in vivo microbiome study) are publicly available in SRA under accession no. PRJNA755974 (Supplementary Table 4).
PubMed id: 37231089
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