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.
PY - 2023/6/1
Y1 - 2023/6/1
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
SN - 2058-5276
VL - 8
SP - 1160
EP - 1175
JO - Nature Microbiology
JF - Nature Microbiology
IS - 6
ER -
