Evolutionary and Functional Analysis of Coagulase Positivity among the Staphylococci.
Evolutionary and Functional Analysis of Coagulase Positivity among the Staphylococci.
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DOI：
10.1128/msphere.00381-21
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发表时间：
2021-08-25
期刊：
影响因子：
4.8
通讯作者：
Fitzgerald JR
中科院分区：
文献类型：
--
作者：
Pickering AC;Yebra G;Gong X;Goncheva MI;Wee BA;MacFadyen AC;Muehlbauer LF;Alves J;Cartwright RA;Paterson GK;Fitzgerald JR
细菌属葡萄球菌包括与一系列宿主物种相关的一大组致病性和非致病性物种。葡萄球菌根据促进血浆凝固的能力分为凝固酶阳性组和凝固酶阴性组，这是一种历史上与引起疾病的能力相关的表型。然而，这种重要的诊断和致病性状在整个属的遗传基础还没有被检查的日期。在这里，我们选择了54个有代表性的葡萄球菌物种和亚种，以检查来自六个代表性的宿主物种的血浆凝固。总共有13种葡萄球菌介导了至少一种宿主种属的血浆凝固，包括一种先前鉴定为凝固酶阴性的宿主种属（条件葡萄球菌）。比较基因组学分析显示，凝固酶活性与编码血管性血友病结合蛋白（vWbp）的基因（vEGF3）的存在相关，而只有金黄色葡萄球菌复合物含有编码葡萄球菌凝固酶（CoA）的基因，葡萄球菌凝固酶是经典的凝血介质。重要的是，S。金黄色葡萄球菌保留vwb依赖性凝固酶活性在一个S.金黄色葡萄球菌中CoA缺失，而假中间葡萄球菌中CoA缺失导致凝固酶活性丧失。基于全基因组的葡萄球菌属的系统发育重建显示，葡萄球菌属的进化过程中，通过突变和重组的等位基因多样化，在至少四个不同的场合获得了vaccine基因。来自选定的凝固酶阳性葡萄球菌的vWbp等位基因变体以宿主依赖性方式介导凝血，表明宿主适应性进化。综上所述，我们已经确定了葡萄球菌凝血的遗传和进化基础，揭示了vWbp是其原型决定因素。重要性某些葡萄球菌促进血浆凝固的能力是致病和诊断的关键特征。在这里，我们提供了一个全面的分析凝固酶阳性的葡萄球菌及其进化的遗传基础。我们表明，冯维勒布兰德结合蛋白，而不是葡萄球菌凝固酶是葡萄球菌的原型凝血因子，并且vaccine基因已获得独立的葡萄球菌的进化过程中的几次。随后，vpn经历了适应性多样化，以促进主机特定的功能。我们的研究结果提供了重要的见解，致病性的演变之间的葡萄球菌和遗传基础的定义诊断表型。
The bacterial genus Staphylococcus comprises a large group of pathogenic and nonpathogenic species associated with an array of host species. Staphylococci are differentiated into coagulase-positive or coagulase-negative groups based on the capacity to promote clotting of plasma, a phenotype historically associated with the ability to cause disease. However, the genetic basis of this important diagnostic and pathogenic trait across the genus has not been examined to date. Here, we selected 54 representative staphylococcal species and subspecies to examine coagulation of plasma derived from six representative host species. In total, 13 staphylococcal species mediated coagulation of plasma from at least one host species including one previously identified as coagulase negative (Staphylococcus condimenti). Comparative genomic analysis revealed that coagulase activity correlated with the presence of a gene (vwb) encoding the von Willebrand binding protein (vWbp) whereas only the Staphylococcus aureus complex contained a gene encoding staphylocoagulase (Coa), the classical mediator of coagulation. Importantly, S. aureus retained vwb-dependent coagulase activity in an S. aureus strain deleted for coa whereas deletion of vwb in Staphylococcus pseudintermedius resulted in loss of coagulase activity. Whole-genome-based phylogenetic reconstruction of the Staphylococcus genus revealed that the vwb gene has been acquired on at least four different occasions during the evolution of the Staphylococcus genus followed by allelic diversification via mutation and recombination. Allelic variants of vWbp from selected coagulase-positive staphylococci mediated coagulation in a host-dependent manner indicative of host-adaptive evolution. Taken together, we have determined the genetic and evolutionary basis of staphylococcal coagulation, revealing vWbp to be its archetypal determinant. IMPORTANCE The ability of some species of staphylococci to promote coagulation of plasma is a key pathogenic and diagnostic trait. Here, we provide a comprehensive analysis of the coagulase positivity of the staphylococci and its evolutionary genetic basis. We demonstrate that the von Willebrand binding protein rather than staphylocoagulase is the archetypal coagulation factor of the staphylococci and that the vwb gene has been acquired several times independently during the evolution of the staphylococci. Subsequently, vwb has undergone adaptive diversification to facilitate host-specific functionality. Our findings provide important insights into the evolution of pathogenicity among the staphylococci and the genetic basis for a defining diagnostic phenotype.