Challagundla Lavanya, Reyes Jinnethe, Rafiqullah Iftekhar, Sordelli Daniel O, Echaniz-Aviles Gabriela, Velazquez-Meza Maria E, Castillo-Ramírez Santiago, Fittipaldi Nahuel, Feldgarden Michael, Chapman Sinéad B, Calderwood Michael S, Carvajal Lina P, Rincon Sandra, Hanson Blake, Planet Paul J, Arias Cesar A, Diaz Lorena, Robinson D Ashley
Department of Data Science, University of Mississippi Medical Center, Jackson, MS, United States.
Molecular Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia.
Front Microbiol. 2018 Aug 22;9:1901. doi: 10.3389/fmicb.2018.01901. eCollection 2018.
Clonal complex 5 methicillin-resistant (CC5-MRSA) includes multiple prevalent clones that cause hospital-associated infections in the Western Hemisphere. Here, we present a phylogenomic study of these MRSA to reveal their phylogeny, spatial and temporal population structure, and the evolution of selected traits. We studied 598 genome sequences, including 409 newly generated sequences, from 11 countries in Central, North, and South America, and references from Asia and Europe. An early-branching CC5-Basal clade is well-dispersed geographically, is methicillin-susceptible and MRSA predominantly of ST5-IV such as the USA800 clone, and includes separate subclades for avian and porcine strains. In the early 1970s and early 1960s, respectively, two clades appeared that subsequently underwent major expansions in the Western Hemisphere: a CC5-I clade in South America and a CC5-II clade largely in Central and North America. The CC5-I clade includes the ST5-I Chilean/Cordobes clone, and the ST228-I South German clone as an early offshoot, but is distinct from other ST5-I clones from Europe that nest within CC5-Basal. The CC5-II clade includes divergent strains of the ST5-II USA100 clone, various other clones, and most known vancomycin-resistant strains of , but is distinct from ST5-II strain N315 from Japan that nests within CC5-Basal. The recombination rate of CC5 was much lower than has been reported for other genetic backgrounds, which indicates that recurrence of vancomycin resistance in CC5 is not likely due to an enhanced promiscuity. An increased number of antibiotic resistances and decreased number of toxins with distance from the CC5 tree root were observed. Of note, the expansions of the CC5-I and CC5-II clades in the Western Hemisphere were preceded by convergent gains of resistance to fluoroquinolone, macrolide, and lincosamide antibiotics, and convergent losses of the staphylococcal enterotoxin p () gene from the immune evasion gene cluster of phage ϕSa3. Unique losses of surface proteins were also noted for these two clades. In summary, our study has determined the relationships of different clades and clones of CC5 and has revealed genomic changes for increased antibiotic resistance and decreased virulence associated with the expansions of these MRSA in the Western Hemisphere.
克隆复合体5型耐甲氧西林金黄色葡萄球菌（CC5-MRSA）包括多个在西半球引起医院相关感染的流行克隆株。在此，我们对这些耐甲氧西林金黄色葡萄球菌进行了系统基因组学研究，以揭示它们的系统发育、时空种群结构以及特定性状的演变。我们研究了来自中美洲、北美洲和南美洲11个国家的598个基因组序列，包括409个新生成的序列，以及来自亚洲和欧洲的参考序列。一个早期分支的CC5-基础分支在地理上分布广泛，对甲氧西林敏感，且主要是ST5-IV型的耐甲氧西林金黄色葡萄球菌，如USA800克隆株，还包括禽类和猪类菌株的独立亚分支。分别在20世纪70年代初和60年代初出现了两个分支，随后在西半球经历了主要的扩张：南美洲的CC5-I分支和主要在中美洲和北美洲的CC5-II分支。CC5-I分支包括ST5-I智利/科尔多瓦克隆株，以及作为早期分支的ST228-I南德克隆株，但与嵌套在CC5-基础分支内的来自欧洲的其他ST5-I克隆株不同。CC5-II分支包括ST5-II USA100克隆株的不同菌株、各种其他克隆株以及大多数已知的耐万古霉素菌株，但与嵌套在CC5-基础分支内的来自日本的ST5-II菌株N315不同。CC5的重组率远低于其他遗传背景下的报道，这表明CC5中万古霉素耐药性的重现不太可能是由于杂交增加所致。观察到随着与CC5树根距离的增加，抗生素耐药性数量增加，毒素数量减少。值得注意的是，在西半球CC5-I和CC5-II分支扩张之前，对氟喹诺酮、大环内酯和林可酰胺类抗生素的耐药性出现了趋同增加，并且噬菌体ϕSa3免疫逃避基因簇中的葡萄球菌肠毒素p（）基因出现了趋同缺失。这两个分支还出现了表面蛋白的独特缺失。总之，我们的研究确定了CC5不同分支和克隆株之间的关系，并揭示了与这些耐甲氧西林金黄色葡萄球菌在西半球扩张相关的抗生素耐药性增加和毒力降低的基因组变化。
