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首页> 外文期刊>mSphere >Phenotypes and Virulence among Staphylococcus aureus USA100, USA200, USA300, USA400, and USA600 Clonal Lineages
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Phenotypes and Virulence among Staphylococcus aureus USA100, USA200, USA300, USA400, and USA600 Clonal Lineages

机译：金黄色葡萄球菌USA100，USA200，USA300，USA400和USA600克隆谱系之间的表型和毒力

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Staphylococcus aureus diseases affect ~500,000 individuals per year in the United States. Worldwide, the USA100, USA200, USA400, and USA600 lineages cause many of the life-threatening S.?aureus infections, such as bacteremia, infective endocarditis, pneumonia, toxic shock syndrome, and surgical site infections. However, the virulence mechanisms associated with these clonal lineages, in particular the USA100 and USA600 isolates, have been severely understudied. We investigated the virulence of these strains, in addition to strains in the USA200, USA300, and USA400 types, in well-established in vitro assays and in vivo in the rabbit model of infective endocarditis and sepsis. We show in the infective endocarditis and sepsis model that strains in the USA100 and USA600 lineages cause high lethality and are proficient in causing native valve infective endocarditis. Strains with high cytolytic activity or producing toxic shock syndrome toxin 1 (TSST-1) or staphylococcal enterotoxin C (SEC) caused lethal sepsis, even with low cytolytic activity. Strains in the USA100, USA200, USA400, and USA600 lineages consistently contained genes that encode for the enterotoxin gene cluster proteins, SEC, or TSST-1 and were proficient at causing infective endocarditis, while the USA300 strains lacked these toxins and were deficient in promoting vegetation growth. The USA100, USA200, and USA400 strains in our collection formed strong biofilms in vitro , whereas the USA200 and USA600 strains exhibited increased blood survival. Hence, infective endocarditis and lethal sepsis are multifactorial and not intrinsic to any one individual clonal group, further highlighting the importance of expanding our knowledge of S.?aureus pathogenesis to clonal lineages causative of invasive disease. IMPORTANCE S.?aureus is the leading cause of infective endocarditis in the developed world, affecting ~40,000 individuals each year in the United States, and the second leading cause of bacteremia (D. R. Murdoch et al., Arch Intern Med 169:463–473, 2009, http://dx.doi.org/10.1001/archinternmed.2008.603 , and H. Wisplinghoff et al., Clin Infect Dis 39:309–317, 2004, http://dx.doi.org/10.1086/421946 ). Even with current medical advances, S.?aureus bloodstream infections and infective endocarditis carry mortality rates of 20 to 66% (S. Y. Tong et al., Clin Microbiol Rev 28:603–661, 2015, http://dx.doi.org/10.1128/CMR.00134-14 ). S.?aureus lineages associated with human disease worldwide include clonal complex 5 (CC5)/USA100, CC30/USA200, CC8/USA300, CC1/USA400, and CC45/USA600. The CC5/USA100, CC30/USA200, and CC45/USA600 lineages cause invasive disease yet remain poorly characterized. USA300 and cytotoxins are central to most S.?aureus virulence studies, and yet, we find evidence that clonal groups are quite heterogeneous in parameters canonically used to measure virulence, including cytotoxicity, biofilm formation, and blood survival, and that the superantigen profile is an important parameter to consider when defining the virulence of S.?aureus strains.
机译：在美国，每年约有500,000个人感染金黄色葡萄球菌疾病。在全球范围内，USA100，USA200，USA400和USA600谱系引起许多威胁生命的金黄色葡萄球菌感染，例如菌血症，感染性心内膜炎，肺炎，中毒性休克综合征和手术部位感染。但是，与这些克隆谱系有关的毒力机制，尤其是USA100和USA600分离株，已被严重研究。我们在完善的体外试验中以及在感染性心内膜炎和脓毒症的兔模型中体内研究了除了USA200，USA300和USA400类型的菌株外，还研究了这些菌株的毒力。我们在感染性心内膜炎和败血症模型中显示，USA100和USA600谱系中的菌株可导致高致死率，并且擅长引起天然瓣膜感染性心内膜炎。具有高溶细胞活性或产生中毒性休克综合症毒素1（TSST-1）或葡萄球菌肠毒素C（SEC）的菌株会导致致命性败血症，即使溶细胞活性较低。 USA100，USA200，USA400和USA600谱系中的菌株始终含有编码肠毒素基因簇蛋白，SEC或TSST-1的基因，并且能够熟练地引起感染性心内膜炎，而USA300菌株却缺乏这些毒素，并且缺乏促进作用。植被生长。我们收集的USA100，USA200和USA400菌株在体外形成了坚固的生物膜，而USA200和USA600菌株则显示出更高的血液存活率。因此，感染性心内膜炎和致死性败血症是多因素的，不是任何一个单独的克隆群体所固有的，这进一步凸显了将我们对金黄色葡萄球菌发病机理的认识扩展到引起侵袭性疾病的克隆谱系的重要性。重要事项金黄色葡萄球菌是发达国家感染性心内膜炎的主要原因，在美国每年约有40,000人感染，是菌血症的第二大主要原因（DR Murdoch等人，Arch Intern Med 169：463-473 ，2009，http：//dx.doi.org/10.1001/archinternmed.2008.603和H.Wisplinghoff等人，Clin Infect Dis 39：309-317，2004，http：//dx.doi.org/10.1086/ 421946）。即使有最新的医学进展，金黄色葡萄球菌的血流感染和感染性心内膜炎的死亡率仍为20％至66％（SY Tong等人，Clin Microbiol Rev 28：603–661，2015，http://dx.doi.org /10.1128/CMR.00134-14）。全球范围内与人类疾病相关的金黄色葡萄球菌谱系包括克隆复合物5（CC5）/ USA100，CC30 / USA200，CC8 / USA300，CC1 / USA400和CC45 / USA600。 CC5 / USA100，CC30 / USA200和CC45 / USA600谱系引起侵袭性疾病，但特征仍然很差。 USA300和细胞毒素是大多数金黄色葡萄球菌毒力研究的中心，但是，我们发现有证据表明，克隆组在规范用于衡量毒力的参数（包括细胞毒性，生物膜形成和血液存活）中具有很大的异质性，并且超抗原谱是定义金黄色葡萄球菌菌株的毒力时要考虑的重要参数。

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