Extracellular DNase MAP3916c attacks the neutrophil extracellular traps and is needed for Mycobacterium avium subsp. paratuberculosis virulence

文献类型： 外文期刊

第一作者： Zang, Xinxin

作者： Zang, Xinxin;Dang, Guanghui;Cai, Zhuming;Shao, Mingzhu;Tang, Yangyang;Cao, Jun;Cui, Ziyin;Liu, Siguo;Tang, Yangyang

作者机构：

关键词： Mycobacterium avium subsp. Paratuberculosis; DNase; MAP3916c; NETs; Virulence factor

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：3.246； 五年影响因子：3.565 ）

ISSN： 0378-1135

年卷期： 2022 年 273 卷

页码：

收录情况： SCI

摘要： Extracellular DNases/nucleases are important virulence factors in many bacteria. However, no DNase/nucleases have been reported in Mycobacterium avium subsp. paratuberculosis (MAP), which is a pathogen of paratuberculosis. Genome analyses of MAP K-10 revealed that the map3916c gene putatively encodes a nuclease. In this study, we show that MAP3916c is an extracellular nonspecific DNase requiring a divalent cation, especially Mg2+. The optimum DNase activity of MAP3916c was exhibited at 41 degrees C and pH 9.0. Site-directed mutagenesis studies indicated that 125-Histidine is necessary for MAP3916c DNase activity. In addition, MAP3916c DNase could destroy the neutrophil extracellular traps (NETs) induced by Phorbol 12-myristate 13-acetate in vitro and degrade the NETs induced by MAP K-10 upon infection. Furthermore, MAP3916c DNase promoted the colonization of MAP K-10, induced the formation of granulomas in the liver and small intestine and promoted the release of IL-1 beta, IL-6 and TNF-alpha inflammatory cytokines during the infection of mice. These results indicated that MAP3916c is relevant to NETs escape and the pathogenicity of MAP. It also provides a basis for further study of the function of nuclease activity on the MAP immune evasion.

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