Details

Autor(en) / Beteiligte

• 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
• Douce, Gillian
• Robinson, Stephen D
• Kroll, J Simon
• Hall, Lindsay J

Titel

Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains

Ist Teil von

• Nature microbiology, 2023-06, Vol.8 (6), p.1160-1175

Ort / Verlag

England

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.