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

Clostridium perfringens Sialidases: Potential Contributors to Intestinal Pathogenesis and Therapeutic Targets.
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DOI:
10.3390/toxins8110341
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发表时间:
2016-11-19
期刊:
影响因子:
4.2
通讯作者:
McClane BA
McClane BA
中科院分区:
医学2区
文献类型:
--
作者:
Li J;Uzal FA;McClane BA

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产气荚膜梭菌是人类和其他动物的组织毒性和肠道感染的主要原因。这种革兰氏阳性厌氧菌可以产生多达三种唾液酸酶,命名为NanH、NanI和NanJ。唾液酸酶在组织毒性感染,如气性坏疽(梭菌性肌坏死)中的作用仍然不明确。然而,最近的体外研究表明,NanI可能通过上调与肠道感染相关的一些毒素的产生,增加其中一些毒素的结合和活性,以及增强C.产气荚膜杆菌转化为肠细胞。NanI对肠道定植的可能贡献进一步得到了C.引起人类急性食物中毒的产气荚膜梭菌菌株通常缺乏nanI基因,而其他产气荚膜梭菌菌株通常缺乏nanI基因。引起人类慢性肠道感染的产气荚膜杆菌菌株通常携带nanI基因。某些唾液酸酶抑制剂已显示阻断NanI活性并减少C.产气荚膜梭菌粘附于培养的肠细胞样细胞,开启了唾液酸酶抑制剂可能是针对C.产气荚膜杆菌肠道感染。这些初步的体外观察结果应使用肠道感染的动物模型来测试其体内意义。
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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