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Toxins 2016, 8(11), 341; doi:10.3390/toxins8110341

Clostridium perfringens Sialidases: Potential Contributors to Intestinal Pathogenesis and Therapeutic Targets

1
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
2
California Animal Health and Food Safety Laboratory, San Bernardino Branch, School of Veterinary Medicine, University of California-Davis, San Bernardino, CA 92408, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Holger Barth
Received: 28 October 2016 / Revised: 10 November 2016 / Accepted: 13 November 2016 / Published: 19 November 2016
(This article belongs to the Special Issue Novel Pharmacological Inhibitors for Bacterial Protein Toxins)
View Full-Text   |   Download PDF [1671 KB, uploaded 19 November 2016]   |  

Abstract

Clostridium perfringens is 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 of C. perfringens to intestinal cells. Possible contributions of NanI to intestinal colonization are further supported by observations that the C. perfringens strains causing acute food poisoning in humans often lack the nanI gene, while other C. perfringens strains causing chronic intestinal infections in humans usually carry a nanI gene. Certain sialidase inhibitors have been shown to block NanI activity and reduce C. perfringens adherence to cultured enterocyte-like cells, opening the possibility that sialidase inhibitors could be useful therapeutics against C. perfringens intestinal infections. These initial in vitro observations should be tested for their in vivo significance using animal models of intestinal infections. View Full-Text
Keywords: Clostridium perfringens; intestinal infections; gas gangrene; toxins; sialidases; sialidase inhibitors Clostridium perfringens; intestinal infections; gas gangrene; toxins; sialidases; sialidase inhibitors
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Li, J.; Uzal, F.A.; McClane, B.A. Clostridium perfringens Sialidases: Potential Contributors to Intestinal Pathogenesis and Therapeutic Targets. Toxins 2016, 8, 341.

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