An update on the human and animal enteric pathogen Clostridium perfringens

Abstract

Clostridium perfringens, a rapid-growing pathogen known to secrete an arsenal of >20 virulent toxins, has been associated with intestinal diseases in both animals and humans throughout the past century. Recent advances in genomic analysis and experimental systems make it timely to re-visit this clinically and veterinary important pathogen. This Review will summarise our understanding of the genomics and virulence-linked factors, including antimicrobial potentials and secreted toxins of this gut pathogen, and then its up-to-date clinical epidemiology and biological role in the pathogenesis of several important human and animal-associated intestinal diseases, including pre-term necrotising enterocolitis. Finally, we highlight some of the important unresolved questions in relation to C. perfringens-mediated infections, and implications for future research directions.

Phylogenomic analysis ofClostridium perfringensidentifies isogenic strains in gastroenteritis outbreaks, and novel virulence-related features

“…Diarrhoea symptoms associated with C. perfringens are primarily due to production of the pore-forming toxin enterotoxin (CPE) by C. perfringens type F strains (2, 60). Additional virulence determinants implicated in diarrhoea include sialidase (NanI), which is linked to enhanced intestinal attachment and an accessory role in enhancing CPE cell-toxicity, and also pore-forming toxin perfringolysin (PFO), a toxin known to act synergistically with alpha-toxin (phospholipase produced by all C. perfringens strains) to inflict intestinal cell damage (24, 61, 62).…”

“…The CPE toxin is responsible for the symptoms of diarrhoea in food poisoning, and non-foodborne illnesses, in the latter usually lasting >3 days, and up to several weeks (2, 66). Genetically, whilst chromosomal encoded cpe strains are primarily linked to food-poisoning (67, 68), non-foodborne diarrhoea is usually associated with plasmid-borne cpe strains (66, 69, 70).…”

“…Genes encoding accessory virulence factors, such as beta-2 toxin, were commonly detected (46.7%; 50/109), and genes encoding phage proteins were also frequently identified, with additional analysis indicating their contribution to increased virulence determinants within the genomes of gastroenteritis-associated C. perfringens . Overall this large-scale genomic study of gastroenteritis-associated C. perfringens suggested that 3 major sub-types underlie these outbreaks: strains carrying (1) pCPF5603 plasmid, (2) pCPF4969 plasmid, and (3) strains carrying cpe on transposable element Tn 5565 (usually integrated into chromosome). Our findings indicate that further studies will be required to fully probe this enteric pathogen, particularly in relation to developing intervention and prevention strategies to reduce food poisoning disease burden in vulnerable patients, such as the elderly.…”

“…Clostridium perfringens is an important pathogen known to cause disease in humans and animals (1, 2). Notably, the pathogenesis of C. perfringens -associated infections is largely attributed to the wide array of toxins this species can produce, with >20 toxins currently identified (3, 4).…”

Molecular structure and function of the carboxy‐terminus of the alpha‐toxin from Clostridium perfringens type A

“…Clostridium perfringens belongs to Gram‐positive bacteria and is widely distributed in various natural environments such as water, soil and also exist in human and animal intestines as a normal intestinal flora (Grenda, Grabczak, Kwiatek, & Bober, ; Kheravii, Swick, Choct, & Wu, ; Kiu & Hall, ). Once humans and animals eat food infected with C. perfringens , they can cause intestinal diseases such as diarrhoea, intestinal toxaemia, haemorrhagic enteritis, food poisoning and gas gangrene (Lacey et al, ; Mwangi, Timmons, Fitz‐Coy, & Parveen, ).…”