Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis.
Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis.
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DOI：
10.3389/fmicb.2020.582437
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发表时间：
2020
影响因子：
5.2
通讯作者：
Kawabata S
中科院分区：
文献类型：
--
作者：
Yamaguchi M;Takemura M;Higashi K;Goto K;Hirose Y;Sumitomo T;Nakata M;Uzawa N;Kawabata S
肺炎链球菌是肺炎、败血症和脑膜炎的主要原因。在此之前，我们通过研究肺炎球菌胆碱结合细胞表面蛋白的进化选择压力，确定了一种新的毒力因子。在此，我们专注于另一种肺炎球菌细胞表面蛋白。含有LPXTG基序的细胞壁锚定蛋白在革兰氏阳性细菌中是保守的。我们的进化分析表明，在所研究的基因，nanA和bgaA有很高比例的密码子下显着的负选择。nanA和bgaA都编码一种多功能糖苷酶，有助于在葡萄糖缺乏的环境中获得营养、肺炎球菌粘附宿主细胞和逃避宿主免疫。然而，一些研究表明，BgaA的作用是有限的，在小鼠肺炎模型，目前还不清楚，如果BgaA影响肺炎球菌在小鼠败血症模型的发病机制。为了评估bgaA的分布和致病性，我们进行了系统发育分析和静脉感染试验。在贝叶斯和最大似然系统发育树中，肺炎球菌bgaA之间的遗传距离很小，并且肺炎球菌bgaA的簇不包含除光州链球菌基因之外的其他细菌直系同源物。进化分析和BgaA结构表明BgaA活性位点不允许改变。小鼠感染试验表明，bgaA的缺失显着降低宿主死亡率。这些结果表明，nanA和bgaA编码进化保守的肺炎球菌毒力因子和分子进化分析可能是一个有用的替代策略，用于确定毒力因子。
Streptococcus pneumoniae is a major cause of pneumonia, sepsis, and meningitis. Previously, we identified a novel virulence factor by investigating evolutionary selective pressure exerted on pneumococcal choline-binding cell surface proteins. Herein, we focus on another pneumococcal cell surface protein. Cell wall-anchoring proteins containing the LPXTG motif are conserved in Gram-positive bacteria. Our evolutionary analysis showed that among the examined genes, nanA and bgaA had high proportions of codon that were under significant negative selection. Both nanA and bgaA encode a multi-functional glycosidase that aids nutrient acquisition in a glucose-poor environment, pneumococcal adherence to host cells, and evasion from host immunity. However, several studies have shown that the role of BgaA is limited in a mouse pneumonia model, and it remains unclear if BgaA affects pneumococcal pathogenesis in a mouse sepsis model. To evaluate the distribution and pathogenicity of bgaA, we performed phylogenetic analysis and intravenous infection assay. In both Bayesian and maximum likelihood phylogenetic trees, the genetic distances between pneumococcal bgaA was small, and the cluster of pneumococcal bgaA did not contain other bacterial orthologs except for a Streptococcus gwangjuense gene. Evolutionary analysis and BgaA structure indicated BgaA active site was not allowed to change. The mouse infection assay showed that the deletion of bgaA significantly reduced host mortality. These results indicated that both nanA and bgaA encode evolutionally conserved pneumococcal virulence factors and that molecular evolutionary analysis could be a useful alternative strategy for identification of virulence factors.
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影响因子：
5.5
作者：
Cornick JE;Tastan Bishop Ö;Yalcin F;Kiran AM;Kumwenda B;Chaguza C;Govindpershad S;Ousmane S;Senghore M;du Plessis M;Pluschke G;Ebruke C;McGee L;Sigaùque B;Collard JM;Bentley SD;Kadioglu A;Antonio M;von Gottberg A;French N;Klugman KP;Heyderman RS;Alderson M;Everett DB;PAGe consortium
通讯作者：
PAGe consortium
影响因子：
3.1
作者：
Blanchette, Krystle A.;Shenoy, Anukul T.;Orihuela, Carlos J.
通讯作者：
Orihuela, Carlos J.
影响因子：
3.6
作者：
King, SJ;Hippe, KR;Weiser, JN
通讯作者：
Weiser, JN
影响因子：
--
作者：
Chen, Austen;Mann, Beth;Paton, James C.
通讯作者：
Paton, James C.
影响因子：
2.1
作者：
Bricker, AL;Camilli, A
通讯作者：
Camilli, A