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Kiu, Raymond, Shaw, Alexander G., Sim, Kathleen, Acuna-Gonzalez, Antia, Price, Christopher A., Bedwell, Harley, Dreger, Sally A., Fowler, Wesley J., Cornwell, Emma, Pickard, Derek, Belteki, Gusztav, Malsom, Jennifer, Phillips, Sarah, Young, Gregory R., Schofield, Zoe, Alcon-Giner, Cristina, Berrington, Janet E., Stewart, Christopher J., Dougan, Gordon, Clarke, Paul 
ORCID: https://orcid.org/0000-0001-6203-7632, Douce, Gillian, Robinson, Stephen D. ORCID: https://orcid.org/0000-0002-6606-7588, Kroll, J. Simon and Hall, Lindsay J. ORCID: https://orcid.org/0000-0001-8938-5709
(2023)
Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains.
Nature Microbiology, 8 (6).
pp. 1160-1175.
ISSN 2058-5276
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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.
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| Additional Information: | Funding 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). We thank the sequencing team at both the Wellcome Trust Sanger Institute and the Quadram Institute Bioscience (QIB) for genome sequencing. We would like to express our appreciation to our colleague S. Carding, and former colleagues S. Caim, L. Harnisch and B. Kirkup at QIB for their discussion on the data and assistance in various training sessions associated with this work. Funding 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). We thank the sequencing team at both the Wellcome Trust Sanger Institute and the Quadram Institute Bioscience (QIB) for genome sequencing. We would like to express our appreciation to our colleague S. Carding, and former colleagues S. Caim, L. Harnisch and B. Kirkup at QIB for their discussion on the data and assistance in various training sessions associated with this work. Publisher Copyright: © 2023, The Author(s). |
| Uncontrolled Keywords: | microbiology,immunology,applied microbiology and biotechnology,genetics,microbiology (medical),cell biology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2404 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Science > Research Groups > Cells and Tissues |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 26 Jun 2023 15:30 |
| Last Modified: | 30 Jan 2024 03:39 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/92498 |
| DOI: | 10.1038/s41564-023-01385-z |
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