Occurrence and Evolution of the Paralogous Zinc Metalloproteases IgA1 Protease, ZmpB, ZmpC, and ZmpD in Streptococcus pneumoniae and Related Commensal Species
Occurrence and Evolution of the Paralogous Zinc Metalloproteases IgA1 Protease, ZmpB, ZmpC, and ZmpD in Streptococcus pneumoniae and Related Commensal Species
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DOI：
10.1128/mbio.00303-12
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发表时间：
2012-09-01
期刊：
影响因子：
6.4
通讯作者：
Kilian, Mogens
中科院分区：
文献类型：
--
作者：
Bek-Thomsen, Malene;Poulsen, Knud;Kilian, Mogens
通过全基因组的计算机分析和对20个种154个代表菌株的活性筛选，研究了肺炎链球菌及其近缘共生种中4种锌金属蛋白酶：IgA1蛋白水解酶、ZmpB、ZmpC和ZmpD的分布、基因组定位和进化。ZMPB普遍存在于链球菌属的Mitis和唾液类群以及Gemella属和Granulicatella属中，但嗜热链球菌中的一个片段基因除外，这是唯一一种非人类栖息地。在肺炎链球菌、假肺炎链球菌、口腔链球菌、血链球菌和溶血双胞菌的所有成员中都观察到了IgA1蛋白酶活性，而在猪链球菌、副血链球菌、猪链球菌、寡发酵链球菌、南方链球菌、波罗河链球菌和猪链球菌中不同程度地存在。对297个ZMP序列和有代表性的看家基因的系统发育分析为肺炎链球菌igA、zmpB和zmpD基因的遗传多样性提供了史无前例的选择，并证明了整个基因和基因组合在种内转移非常频繁。据推测，由于它们对共生生活方式的适应，在很大程度上不受适应性粘膜免疫因子的影响，共生链球菌中的相应基因保持保守。这种广泛的分布和显著的序列多样性表明，锌金属蛋白酶的古老起源早于类人物种的出现。ZmpB似乎是人类的祖先基因，后来被复制并成功地多样化成不同的功能，很可能与人类宿主相关的一个重要但未知的管家功能。重要的是，与ZMPB、ZMPC和ZMPD同源的锌金属蛋白酶IgA1蛋白酶、ZMPB、ZMPC和ZMPD已被鉴定为对人类病原体肺炎链球菌的毒力至关重要。这项研究定位了肺炎链球菌和链球菌属、双球菌属和颗粒菌属相关共生物种中相应基因和酶活性的存在。分布、基因组定位和序列多样性表明，zmpB是在今天的类人物种进化之前的祖先基因。ZmpB蛋白酶可能在Mitis和唾液链球菌与其人类宿主的联系中发挥重要但尚未确定的作用，因为它在这两个群体中普遍存在，除了嗜热链球菌中的一个片段基因，这是唯一与人类无关的物种。IgA1蛋白酶、ZmpB和ZmpD的相对序列多样化是肺炎链球菌与密切相关的共生链球菌在选择这些表面暴露蛋白多样化方面存在差异的显著证据。
The distribution, genome location, and evolution of the four paralogous zinc metalloproteases, IgA1 protease, ZmpB, ZmpC, and ZmpD, in Streptococcus pneumoniae and related commensal species were studied by in silico analysis of whole genomes and by activity screening of 154 representatives of 20 species. ZmpB was ubiquitous in the Mitis and Salivarius groups of the genus Streptococcus and in the genera Gemella and Granulicatella, with the exception of a fragmented gene in Streptococcus thermophilus, the only species with a nonhuman habitat. IgA1 protease activity was observed in all members of S. pneumoniae, S. pseudopneumoniae, S. oralis, S. sanguinis, and Gemella haemolysans, was variably present in S. mitis and S. infantis, and absent in S. gordonii, S. parasanguinis, S. cristatus, S. oligofermentans, S. australis, S. peroris, and S. suis. Phylogenetic analysis of 297 zmp sequences and representative housekeeping genes provided evidence for an unprecedented selection for genetic diversification of the iga, zmpB, and zmpD genes in S. pneumoniae and evidence of very frequent intraspecies transfer of entire genes and combination of genes. Presumably due to their adaptation to a commensal lifestyle, largely unaffected by adaptive mucosal immune factors, the corresponding genes in commensal streptococci have remained conserved. The widespread distribution and significant sequence diversity indicate an ancient origin of the zinc metalloproteases predating the emergence of the humanoid species. zmpB, which appears to be the ancestral gene, subsequently duplicated and successfully diversified into distinct functions, is likely to serve an important but yet unknown housekeeping function associated with the human host.IMPORTANCE The paralogous zinc metalloproteases IgA1 protease, ZmpB, ZmpC, and ZmpD have been identified as crucial for virulence of the human pathogen Streptococcus pneumoniae. This study maps the presence of the corresponding genes and enzyme activities in S. pneumoniae and in related commensal species of the genera Streptococcus, Gemella, and Granulicatella. The distribution, genome location, and sequence diversification indicate that zmpB is the ancestral gene predating the evolution of today's humanoid species. The ZmpB protease may play an important but yet unidentified role in the association of streptococci of the Mitis and Salivarius groups with their human host, as it is ubiquitous in these two groups, except for a fragmented gene in Streptococcus thermophilus, the only species not associated with humans. The relative sequence diversification of the IgA1 protease, ZmpB, and ZmpD is striking evidence of differences in selection for diversification of these surface-exposed proteins in the pathogen S. pneumoniae compared to the closely related commensal streptococci.