Nicotinamide Adenine Dinucleotide-Dependent Flavin Oxidoreductase of Mycoplasma hyopneumoniae Functions as a Potential Novel Virulence Factor and Not Only as a Metabolic Enzyme.
Nicotinamide Adenine Dinucleotide-Dependent Flavin Oxidoreductase of Mycoplasma hyopneumoniae Functions as a Potential Novel Virulence Factor and Not Only as a Metabolic Enzyme.
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猪肺炎支原体的烟酰胺腺嘌呤二核苷酸依赖性黄素氧化还原酶不仅作为代谢酶，而且作为潜在的新型毒力因子发挥作用
DOI：
10.3389/fmicb.2021.747421
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发表时间：
2021
影响因子：
5.2
通讯作者：
Feng Z
中科院分区：
文献类型：
--
作者：
Xie X;Hao F;Chen R;Wang J;Wei Y;Liu J;Wang H;Zhang Z;Bai Y;Shao G;Xiong Q;Feng Z
猪肺炎支原体（Mhp）是引起地方性肺炎的主要病原体，地方性肺炎是一种对全球养猪业产生重大影响的疾病。地方性肺炎的发病机制，特别是可能的毒力因子Mhp，仍然没有完全阐明。转录组和蛋白质组学分析的不同Mhp菌株在文献中报道的毒力的差异，高和低毒力菌株之间的RNA转录水平的差异最初表明，烟酰胺腺嘌呤二核苷酸（NADH）依赖的黄素氧化还原酶（NFOR）与Mhp的致病性。对Mhp中的NFOR蛋白进行原核表达和纯化，制备兔源性抗NFOR多克隆抗体，并对Mhp NFOR进行多序列比对和进化分析。首次发现NFOR蛋白在所有Mhp菌株中是保守的，并且NFOR定位于细胞表面，并且可以粘附于永生化猪支气管上皮细胞（hTERT-PBECs）。粘附hTERT-PBECs可以特异性地抑制抗NFOR多克隆抗体，和粘附率高，低毒力菌株，168和168 L，显着下降了40%以上。此外，Mhp NFOR不仅识别并与宿主纤连蛋白和纤溶酶原相互作用，而且还诱导hTERT-PBECs的细胞氧化应激和凋亡。与Mhp NFOR共同孵育的hTERT-PBECs释放乳酸脱氢酶的量与Mhp的毒力呈显著正相关。总体而言，NFOR除了是一种与氧化应激相关的代谢酶外，还可能是Mhp的一种潜在的新型毒力因子，从而参与了Mhp的致病过程，为研究其他支原体的致病机制提供了新的思路和理论支持。
Mycoplasma hyopneumoniae (Mhp) is the main pathogen that causes enzootic pneumonia, a disease that has a significant impact on the pig industry worldwide. The pathogenesis of enzootic pneumonia, especially possible virulence factors of Mhp, has still not been fully elucidated. The transcriptomic and proteomic analyses of different Mhp strains reported in the literature have revealed differences in virulence, and differences in RNA transcription levels between high- and low-virulence strains initially indicated that nicotinamide adenine dinucleotide (NADH)-dependent flavin oxidoreductase (NFOR) was related to Mhp pathogenicity. Prokaryotic expression and purification of the NFOR protein from Mhp were performed, a rabbit-derived polyclonal antibody against NFOR was prepared, and multiple sequence alignment and evolutionary analyses of Mhp NFOR were performed. For the first time, it was found that the NFOR protein was conserved among all Mhp strains, and NFOR was localized to the cell surface and could adhere to immortalized porcine bronchial epithelial cells (hTERT-PBECs). Adhesion to hTERT-PBECs could be specifically inhibited by an anti-NFOR polyclonal antibody, and the rates of adhesion to both high- and low-virulence strains, 168 and 168L, significantly decreased by more than 40%. Moreover, Mhp NFOR not only recognized and interacted with host fibronectin and plasminogen but also induced cellular oxidative stress and apoptosis in hTERT-PBECs. The release of lactate dehydrogenase by hTERT-PBECs incubated with Mhp NFOR was significantly positively correlated with the virulence of Mhp. Overall, in addition to being a metabolic enzyme related to oxidative stress, NFOR may also function as a potential novel virulence factor of Mhp, thus contributing to the pathogenesis of Mhp; these findings provide new ideas and theoretical support for studying the pathogenic mechanisms of other mycoplasmas.
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影响因子：
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作者：
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