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1.
Nat Microbiol ; 8(6): 1160-1175, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37231089

RESUMO

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.


Assuntos
Clostridium perfringens , Doenças do Recém-Nascido , Lactente , Recém-Nascido , Humanos , Animais , Camundongos , Clostridium perfringens/genética , Recém-Nascido Prematuro , Estudos Retrospectivos , Virulência/genética , Genômica
2.
Anaerobe ; 80: 102713, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36754140

RESUMO

Prophylactic administration of oral probiotics is associated with significant reductions in the morbidity and mortality of necrotising enterocolitis in preterm infants. We document the first case of Bifidobacterium longum subsp. infantis sub-clinical bacteraemia, in an extremely low birth weight preterm infant, since introduction of routine probiotic treatment at the Norfolk and Norwich University Hospital 10 years ago. Whole genome comparisons confirmed the isolated strain likely originated from the probiotic product.


Assuntos
Bacteriemia , Probióticos , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Bifidobacterium/genética , Bacteriemia/diagnóstico , Bifidobacterium longum subspecies infantis
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