TY - JOUR
T1 - Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains
AU - Kiu, Raymond
AU - Shaw, Alexander G.
AU - Sim, Kathleen
AU - Acuna-Gonzalez, Antia
AU - Price, Christopher A.
AU - Bedwell, Harley
AU - Dreger, Sally A.
AU - Fowler, Wesley J.
AU - Cornwell, Emma
AU - Pickard, Derek
AU - Belteki, Gusztav
AU - Malsom, Jennifer
AU - Phillips, Sarah
AU - Young, Gregory R.
AU - Schofield, Zoe
AU - Alcon-Giner, Cristina
AU - Berrington, Janet E.
AU - Stewart, Christopher J.
AU - Dougan, Gordon
AU - Clarke, Paul
AU - Douce, Gillian
AU - Robinson, Stephen D.
AU - Kroll, J. Simon
AU - Hall, Lindsay J.
N1 - 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.
PY - 2023/5/25
Y1 - 2023/5/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85160280187&partnerID=8YFLogxK
U2 - 10.1038/s41564-023-01385-z
DO - 10.1038/s41564-023-01385-z
M3 - Article
C2 - 37231089
AN - SCOPUS:85160280187
VL - 8
SP - 1160
EP - 1175
JO - Nature Microbiology
JF - Nature Microbiology
SN - 2058-5276
IS - 6
ER -
