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

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          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.

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          Most cited references 54

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          Clostridial enteric diseases of domestic animals.

           J Songer (1996)
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            Skewed genomic variability in strains of the toxigenic bacterial pathogen, Clostridium perfringens.

            Clostridium perfringens is a Gram-positive, anaerobic spore-forming bacterium commonly found in soil, sediments, and the human gastrointestinal tract. C. perfringens is responsible for a wide spectrum of disease, including food poisoning, gas gangrene (clostridial myonecrosis), enteritis necroticans, and non-foodborne gastrointestinal infections. The complete genome sequences of Clostridium perfringens strain ATCC 13124, a gas gangrene isolate and the species type strain, and the enterotoxin-producing food poisoning strain SM101, were determined and compared with the published C. perfringens strain 13 genome. Comparison of the three genomes revealed considerable genomic diversity with >300 unique "genomic islands" identified, with the majority of these islands unusually clustered on one replichore. PCR-based analysis indicated that the large genomic islands are widely variable across a large collection of C. perfringens strains. These islands encode genes that correlate to differences in virulence and phenotypic characteristics of these strains. Significant differences between the strains include numerous novel mobile elements and genes encoding metabolic capabilities, strain-specific extracellular polysaccharide capsule, sporulation factors, toxins, and other secreted enzymes, providing substantial insight into this medically important bacterial pathogen.
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              Structure, function and metabolism of sialic acids

               C Traving,  R. Schauer (1998)
              Abstract. Sialic acids represent a family of sugar molecules with an unusual and highly variable chemical structure that are found mostly in the terminal position of oligosaccharide chains on the surface of cells and molecules. These special features enable them to fulfil several important and even diametrical biological functions. Because of the great importance of sialic acids, it is also worth having a look at their metabolism in order to get an idea of the intimate connection between structure and function of these fascinating molecules and the often serious consequences that result from disturbances in the balance of metabolic reactions. The latter can be due to genetic disorders that result in the absence of certain enzyme activity, leading to severe illness or even to death.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                19 November 2016
                November 2016
                : 8
                : 11
                Affiliations
                [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; jihongli@ 123456pitt.edu
                [2 ]California Animal Health and Food Safety Laboratory, San Bernardino Branch, School of Veterinary Medicine, University of California-Davis, San Bernardino, CA 92408, USA; fauzal@ 123456ucdavis.edu
                Author notes
                [* ]Correspondence: bamcc@ 123456pitt.edu ; Tel.: +1-412-648-9022
                Article
                toxins-08-00341
                10.3390/toxins8110341
                5127137
                27869757
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

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