title: Clostridium perfringens Sialidases: Potential Contributors to Intestinal Pathogenesis and Therapeutic Targets.
abstract: Clostridium perfringensis a major cause of histotoxic and intestinal infections of humans and other animals. This Gram-positive anaerobic bacterium can produce up to three sialidases named NanH, NanI, and NanJ. The role of sialidases in histotoxic infections, such as gas gangrene (clostridial myonecrosis), remains equivocal. However, recent in vitro studies suggest that NanI may contribute to intestinal virulence by upregulating production of some toxins associated with intestinal infection, increasing the binding and activity of some of those toxins, and enhancing adherence ofC. perfringensto intestinal cells. Possible contributions of NanI to intestinal colonization are further supported by observations that theC. perfringensstrains causing acute food poisoning in humans often lack thenanIgene, while otherC. perfringensstrains causing chronic intestinal infections in humans usually carry ananIgene. Certain sialidase inhibitors have been shown to block NanI activity and reduceC. perfringensadherence to cultured enterocyte-like cells, opening the possibility that sialidase inhibitors could be useful therapeutics againstC. perfringensintestinal infections. These initial in vitro observations should be tested for their in vivo significance using animal models of intestinal infections.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Room 420, Bridgeside Point II Building, 450 Technology Drive, Pittsburgh, PA 15219, USA. jihongli@pitt.edu.
authors.forename: Jihong
authors.initials: J
authors.lastname: Li
authors.affiliation: California Animal Health and Food Safety Laboratory, San Bernardino Branch, School of Veterinary Medicine, University of California-Davis, San Bernardino, CA 92408, USA. fauzal@ucdavis.edu.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Uzal
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Room 420, Bridgeside Point II Building, 450 Technology Drive, Pittsburgh, PA 15219, USA. bamcc@pitt.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: McClane
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000235:genetics; D003015:Clostridium Infections / Q000188:drug therapy / Q000201:enzymology; D003016:Clostridium perfringens / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D007410:Intestinal Diseases / Q000188:drug therapy / Q000201:enzymology; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000235:genetics; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D009439:Neuraminidase
keywords: Clostridium perfringens; gas gangrene; intestinal infections; sialidase inhibitors; sialidases; toxins