Phenotypes and Virulence among Staphylococcus aureus USA100, USA200, USA300, USA400, and USA600 Clonal Lineages.
Phenotypes and Virulence among Staphylococcus aureus USA100, USA200, USA300, USA400, and USA600 Clonal Lineages.
复制标题
DOI：
10.1128/msphere.00071-16
复制
发表时间：
2016-05
期刊：
影响因子：
4.8
通讯作者：
Salgado-Pabón W
中科院分区：
文献类型：
--
作者：
King JM;Kulhankova K;Stach CS;Vu BG;Salgado-Pabón W
金黄色葡萄球菌是发达国家感染性心内膜炎的主要原因，每年在美国影响约40,000人，以及菌血症的第二大原因(D.R.Murdoch等人，Arch Intern Med169：463-473,2009，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).即使在目前的医学进步下，金黄色葡萄球菌血流感染和感染性心内膜炎的死亡率仍高达20%至66%(S.Y.童等人，临床微生物版28：603-661,2015，http://dx.doi.org/10.1128/CMR.00134-14).全球与人类疾病相关的金黄色葡萄球菌谱系包括克隆复合体5(CC5)/USA100、CC30/USA200、CC8/USA300、CC1/USA400和CC45/USA600。CC5/USA100、CC30/USA200和CC45/USA600谱系导致侵袭性疾病，但仍缺乏特征性。USA300和细胞毒素是大多数金黄色葡萄球菌毒力研究的核心，然而，我们发现有证据表明，克隆群体在衡量毒力的经典参数上相当不同，包括细胞毒性、生物膜形成和血液存活，并且超抗原图谱是定义金黄色葡萄球菌毒力时要考虑的一个重要参数。在美国，金黄色葡萄球菌疾病每年影响约500,000人。在世界范围内，USA100、USA200、USA400和USA600谱系导致许多危及生命的金黄色葡萄球菌感染，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。然而，与这些克隆谱系相关的毒力机制，特别是USA100和USA600分离物，一直被严重研究不足。除了USA200、USA300和USA400型菌株外，我们还在兔感染性心内膜炎和败血症模型上进行了成熟的体外和体内试验，调查了这些菌株的毒力。我们在感染性心内膜炎和脓毒症模型中表明，USA100和USA600谱系中的菌株可导致高致死率，并熟练地导致自然瓣膜感染性心内膜炎。高溶细胞性或产生中毒性休克综合征毒素1(TSST-1)或葡萄球菌肠毒素C(SEC)的菌株可导致致死性脓毒症，即使低溶细胞性也可引起。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，并且擅长引起感染性心内膜炎，而USA300菌株缺乏这些毒素，在促进植物生长方面也存在缺陷。我们收集的USA100、USA200和USA400菌株在体外形成了强大的生物膜，而USA200和USA600菌株表现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，而不是任何一个个体克隆组固有的，这进一步突出了将我们对金黄色葡萄球菌致病机制的知识扩展到导致侵袭性疾病的克隆谱系的重要性。重要性金黄色葡萄球菌是发达国家感染性心内膜炎的主要原因，每年在美国影响约40,000人，并是菌血症的第二大原因(D.R.Murdoch等人，Arch Intern Med169：463-473,2009，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).即使在目前的医学进步下，金黄色葡萄球菌血流感染和感染性心内膜炎的死亡率仍高达20%至66%(S.Y.童等人，临床微生物版28：603-661,2015，http://dx.doi.org/10.1128/CMR.00134-14).全球与人类疾病相关的金黄色葡萄球菌谱系包括克隆复合体5(CC5)/USA100、CC30/USA200、CC8/USA300、CC1/USA400和CC45/USA600。CC5/USA100、CC30/USA200和CC45/USA600谱系导致侵袭性疾病，但仍缺乏特征性。USA300和细胞毒素是大多数金黄色葡萄球菌毒力研究的核心，然而，我们发现有证据表明，克隆群体在衡量毒力的经典参数上相当不同，包括细胞毒性、生物膜形成和血液存活，并且超抗原图谱是定义金黄色葡萄球菌毒力时要考虑的一个重要参数。
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. 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.