Abstract
The clostridia produce an arsenal of toxins to facilitate their survival within the host environment. TcsL is one of two major toxins produced by Clostridium sordellii, a human and animal pathogen, and is essential for disease pathogenesis of this bacterium. C. sordellii produces many other toxins, but the role that they play in disease is not known, although previous work has suggested that the sialidase enzyme NanS may be involved in the characteristic leukemoid reaction that occurs during severe disease. In this study we investigated the role of NanS in C. sordellii disease pathogenesis. We constructed a nanS mutant and showed that NanS is the only sialidase produced from C. sordellii strain ATCC9714 since sialidase activity could not be detected from the nanS mutant. Complementation with the wild-type gene restored sialidase production to the nanS mutant strain. Cytotoxicity assays using sialidase-enriched culture supernatants applied to gut (Caco2), vaginal (VK2), and cervical cell lines (End1/E6E7 and Ect1/E6E7) showed that NanS was not cytotoxic to these cells. However, the cytotoxic capacity of a toxin-enriched supernatant to the vaginal and cervical cell lines was substantially enhanced in the presence of NanS. TcsL was not the mediator of the observed cytotoxicity since supernatants harvested from a TcsL-deficient strain displayed similar cytotoxicity levels to TcsL-containing supernatants. This study suggests that NanS works synergistically with an unknown toxin or toxins to exacerbate C. sordellii-mediated tissue damage in the host.
Highlights
Clostridium sordellii is a Gram positive, spore-forming anaerobe, and an important pathogen of humans and animals that causes a range of severe diseases [1,2,3,4]
All C. sordellii strains used in this study were derivatives of ATCC9714 (Table 1) and were cultured either in Heart infusion broth (HIS) (Oxoid) supplemented with 0.1% L-cysteine HCL and 0.5%
The nanS gene is present in all C. sordellii isolates [26] and NanS is considered to be a virulence factor of this bacterium, which may contribute to the characteristic leukemoid reaction that is associated with fatal cases of disease [5]
Summary
Clostridium sordellii is a Gram positive, spore-forming anaerobe, and an important pathogen of humans and animals that causes a range of severe diseases [1,2,3,4]. Sialidase-mediated virulence mechanisms vary and include the enhancement of biofilm formation [20], increased bacterial adherence to host cells [10,16], and augmenting the cytotoxicity of specific toxins [16,17,21,22]. C. sordellii encodes at least one sialidase, NanS [1,7,26], which has been hypothesised to play a role in cell adhesion and/or the enhanced cytotoxicity of its various toxins within the sialic acid-containing gastrointestinal tract and vaginal host niches. NanS does not appear to enhance TcsL activity, it augments the action of an unknown virulence factor produced by strain ATCC9714 on host cells, since cell cytotoxicity was enhanced in the presence of sialidase
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