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Published on: December 10, 2016
Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens
Raymond Kiu1, Alexander G Shaw2, Kathleen Sim2
1Gut Microbes and Health, Quadram Institute Bioscience, Norwich, UK.
Insights
Clostridium perfringens strains producing the perfringolysin O toxin (pfoA+) are linked to severe infant gut disease. These pfoA+ strains demonstrate greater virulence in vitro and in vivo, highlighting their role in necrotizing enterocolitis.
Area of Science:
- Microbiology
- Genomics
- Neonatal Medicine
Background:
- Clostridium perfringens is an anaerobic, toxin-producing bacterium implicated in intestinal diseases.
- Recent infant gut microbiome studies link C. perfringens to necrotizing enterocolitis (NEC), particularly in preterm infants (CPA-NEC).
Purpose of the Study:
- To investigate the genomic characteristics and pathogenic traits of C. perfringens isolates from preterm infants.
- To determine the role of specific virulence factors, like perfringolysin O (pfoA), in C. perfringens-associated NEC.
Main Methods:
- Whole-genome sequencing of 272 C. perfringens isolates from 70 UK infants.
- Genomic analyses including virulence profiling, strain tracking, and plasmid analysis.
- Experimental characterization of pathogenic traits in vitro and in vivo using a murine model.
Main Results:
- A hypovirulent lineage of C. perfringens was identified with deficiency in the pfoA gene and certain colonization factors.
- pfoA-positive (pfoA+) infant-associated strains exhibited significantly greater cellular damage in vitro compared to pfoA-negative (pfoA-) strains.
- The enhanced virulence of pfoA+ strains was confirmed in vivo using a C57BL/6 murine model.
Conclusions:
- pfoA+ C. perfringens strains are significant gut pathogens in preterm infants, contributing to CPA-NEC.
- The presence or absence of pfoA is a key determinant of C. perfringens virulence in this context.
- Findings suggest potential targets for therapeutic interventions against C. perfringens in preterm infants.
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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