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

Jihong Li,Francisco Uzal,Bruce Mcclane

doi:10.3390/toxins8110341

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.

Highlights

NanI itself does not appear to be a significant adhesin since the CN3718 codY null mutant shows 50% less adherence to Caco‐2 cells compared to wild‐type CN3718, despite this mutant mutant shows 50% less adherence to Caco-2 cells compared to wild-type CN3718, despite this mutant producing the same levels of NanI as the wild‐type strain [45]
A few in vivo studies have far examined the role of exoenzymes in C. perfringens pathogenesis and their results have been equivocal
Those studies examined the possible role of sialidases in gas gangrene

Summary

An Introduction to Clostridium perfringens

Clostridium perfringens is present throughout the environment, including soil, sewage, feces, foods, and the normal gastrointestinal flora of animals [1,2]. Inactivating the nanI gene in C. perfringens type A strain 13 caused a slight increase in supernatant activities of alpha toxin and perfringolysin O (PFO), which are contributors to gas gangrene [37], but their role (if any) in most intestinal infections, human infections, is unsettled [3]. While NanI can enhance C. perfringens adherence and toxin binding, typical type A FP strains, i.e., those with a chromosomal cpe gene, do not carry the nanI gene. Those typical FP strains possess very low exosialidase activities [36].

Sialidase Inhibitors

Findings

Concluding Remarks and Future Directions