Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains (original) (raw)
Kiu, R. et al. (2023) Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains.Nature Microbiology, 8(6), pp. 1160-1175. (doi: 10.1038/s41564-023-01385-z) (PMID:37231089) (PMCID:PMC10234813)
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.
| Item Type: | Articles |
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| Additional Information: | This research was supported in part by the NBI Computing infrastructure for Science (CiS) group through the provision of a high-performance computing cluster. L.J.H. is supported by: Wellcome Trust Investigator Awards (nos. 100974/C/13/Z and 220876/Z/20/Z); the Biotechnology and Biological Sciences Research Council (BBSRC), Institute Strategic Programme Gut Microbes and Health BB/R012490/1, and its constituent projects BBS/E/ F/000PR10353 and BBS/E/F/000PR10356. D.P. was funded by the Wellcome Trust. C.J.S. is supported by the Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (no. 221745/Z/20/Z). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Douce, Dr Gillian |
| Creator Roles: | Douce, G.Conceptualization |
| Authors: | Kiu, R., Shaw, A. G., Sim, K., Acuna-Gonzalez, A., Price, C. A., Bedwell, H., Dreger, S. A., Fowler, W. J., Cornwell, E., Pickard, D., Belteki, G., Malsom, J., Phillips, S., Young, G. R., Schofield, Z., Alcon-Giner, C., Berrington, J. E., Stewart, C. J., Dougan, G., Clarke, P., Douce, G., Robinson, S. D., Kroll, J. S., and Hall, L. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Nature Microbiology |
| Publisher: | Nature Research |
| ISSN: | 2058-5276 |
| ISSN (Online): | 2058-5276 |
| Published Online: | 25 May 2023 |
| Copyright Holders: | Copyright: © The Author(s) 2023 |
| First Published: | First published in Nature Microbiology 8(6): 1160-1175, |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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Deposit and Record Details
| ID Code: | 299974 |
|---|---|
| Depositing User: | Publications Router |
| Datestamp: | 07 Aug 2024 09:31 |
| Last Modified: | 04 Sep 2024 09:29 |
| Date of acceptance: | 17 April 2023 |
| Date of first online publication: | 25 May 2023 |
| Date Deposited: | 7 August 2024 |
| Data Availability Statement: | Yes |