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.

Nature Microbiology
|May 25, 2023
PubMed

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.

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