Herron-Olson Lisa, Fitzgerald J Ross, Musser James M, Kapur Vivek
Department of Microbiology, Veterinary Pathobiology and Biomedical Genomics Center, University of Minnesota, Saint Paul, Minnesota, United States of America.
PLoS One. 2007 Oct 31;2(10):e1120. doi: 10.1371/journal.pone.0001120.
The majority of Staphylococcus aureus isolates that are recovered from either serious infections in humans or from mastitis in cattle represent genetically distinct sets of clonal groups. Moreover, population genetic analyses have provided strong evidence of host specialization among S. aureus clonal groups associated with human and ruminant infection. However, the molecular basis of host specialization in S. aureus is not understood.
METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the genome of strain ET3-1, a representative isolate of a common bovine mastitis-causing S. aureus clone. Strain ET3-1 encodes several genomic elements that have not been previously identified in S. aureus, including homologs of virulence factors from other gram-positive pathogens. Relative to the other sequenced S. aureus associated with human infection, allelic variation in ET3-1 was high among virulence and surface-associated genes involved in host colonization, toxin production, iron metabolism, antibiotic resistance, and gene regulation. Interestingly, a number of well-characterized S. aureus virulence factors, including protein A and clumping factor A, exist as pseudogenes in ET3-1. Whole-genome DNA microarray hybridization revealed considerable similarity in the gene content of highly successful S. aureus clones associated with bovine mastitis, but not among those clones that are only infrequently recovered from bovine hosts.
CONCLUSIONS/SIGNIFICANCE: Whole genome sequencing and comparative genomic analyses revealed a set of molecular genetic features that distinguish clones of highly successful bovine-associated S. aureus optimized for mastitis pathogenesis in cattle from those that infect human hosts or are only infrequently recovered from bovine sources. Further, the results suggest that modern bovine specialist clones diverged from a common ancestor resembling human-associated S. aureus clones through a combination of foreign DNA acquisition and gene decay.
从人类严重感染或牛乳腺炎中分离出的大多数金黄色葡萄球菌菌株代表了基因上不同的克隆群。此外，群体遗传学分析提供了强有力的证据，表明与人类和反刍动物感染相关的金黄色葡萄球菌克隆群之间存在宿主特异性。然而，金黄色葡萄球菌宿主特异性的分子基础尚不清楚。
方法/主要发现：我们对ET3-1菌株的基因组进行了测序，ET3-1是一种常见的引起牛乳腺炎的金黄色葡萄球菌克隆的代表性分离株。ET3-1菌株编码了几种以前在金黄色葡萄球菌中未被鉴定的基因组元件，包括来自其他革兰氏阳性病原体的毒力因子同源物。相对于其他与人类感染相关的已测序金黄色葡萄球菌，ET3-1在参与宿主定植、毒素产生、铁代谢、抗生素抗性和基因调控的毒力和表面相关基因中，等位基因变异很高。有趣的是，一些特征明确的金黄色葡萄球菌毒力因子，包括蛋白A和凝聚因子A，在ET3-1中以假基因的形式存在。全基因组DNA微阵列杂交显示，与牛乳腺炎相关的高度成功的金黄色葡萄球菌克隆的基因含量有相当大的相似性，但在那些很少从牛宿主中分离出的克隆中则没有。
结论/意义：全基因组测序和比较基因组分析揭示了一组分子遗传特征，这些特征将高度成功的与牛相关的金黄色葡萄球菌克隆与那些感染人类宿主或很少从牛源分离出的克隆区分开来，这些克隆是为牛乳腺炎发病机制而优化的。此外，结果表明现代牛特异性克隆通过外源DNA获取和基因衰变的组合，从类似于人类相关金黄色葡萄球菌克隆的共同祖先中分化出来。
