Cabot Gabriel, López-Causapé Carla, Ocampo-Sosa Alain A, Sommer Lea M, Domínguez María Ángeles, Zamorano Laura, Juan Carlos, Tubau Fe, Rodríguez Cristina, Moyà Bartolomé, Peña Carmen, Martínez-Martínez Luis, Plesiat Patrick, Oliver Antonio
Servicio de Microbiología and Unidad de Investigación, Hospital Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain.
Servicio de Microbiología, Hospital Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla, Santander, Spain.
Antimicrob Agents Chemother. 2016 Nov 21;60(12):7415-7423. doi: 10.1128/AAC.01720-16. Print 2016 Dec.
Whole-genome sequencing (WGS) was used for the characterization of the frequently extensively drug resistant (XDR) Pseudomonas aeruginosa sequence type 175 (ST175) high-risk clone. A total of 18 ST175 isolates recovered from 8 different Spanish hospitals were analyzed; 4 isolates from 4 different French hospitals were included for comparison. The typical resistance profile of ST175 included penicillins, cephalosporins, monobactams, carbapenems, aminoglycosides, and fluoroquinolones. In the phylogenetic analysis, the four French isolates clustered together with two isolates from one of the Spanish regions. Sequence variation was analyzed for 146 chromosomal genes related to antimicrobial resistance, and horizontally acquired genes were explored using online databases. The resistome of ST175 was determined mainly by mutational events; resistance traits common to all or nearly all of the strains included specific ampR mutations leading to ampC overexpression, specific mutations in oprD conferring carbapenem resistance, or a mexZ mutation leading to MexXY overexpression. All isolates additionally harbored an aadB gene conferring gentamicin and tobramycin resistance. Several other resistance traits were specific to certain geographic areas, such as a streptomycin resistance gene, aadA13, detected in all four isolates from France and in the two isolates from the Cantabria region and a glpT mutation conferring fosfomycin resistance, detected in all but these six isolates. Finally, several unique resistance mutations were detected in single isolates; particularly interesting were those in genes encoding penicillin-binding proteins (PBP1A, PBP3, and PBP4). Thus, these results provide information valuable for understanding the genetic basis of resistance and the dynamics of the dissemination and evolution of high-risk clones.
全基因组测序（WGS）用于对频繁出现的广泛耐药（XDR）铜绿假单胞菌序列类型175（ST175）高危克隆进行特征分析。对从8家不同西班牙医院分离出的18株ST175菌株进行了分析；还纳入了从4家不同法国医院分离出的4株菌株用于比较。ST175的典型耐药谱包括青霉素类、头孢菌素类、单环β-内酰胺类、碳青霉烯类、氨基糖苷类和氟喹诺酮类。在系统发育分析中，4株法国分离株与来自西班牙一个地区的2株分离株聚在一起。对146个与抗菌药物耐药性相关的染色体基因进行了序列变异分析，并使用在线数据库探索了水平获得的基因。ST175的耐药基因组主要由突变事件决定；所有或几乎所有菌株共有的耐药特征包括导致ampC过表达的特定ampR突变、赋予碳青霉烯耐药性的oprD特定突变或导致MexXY过表达的mexZ突变。所有分离株还携带一个赋予庆大霉素和妥布霉素耐药性的aadB基因。其他一些耐药特征在某些地理区域具有特异性，例如在来自法国的所有4株分离株以及来自坎塔布里亚地区的2株分离株中检测到的链霉素耐药基因aadA13，以及在除这6株分离株外的所有分离株中检测到的赋予磷霉素耐药性的glpT突变。最后，在单个分离株中检测到了几个独特的耐药突变；特别有趣的是那些编码青霉素结合蛋白（PBP1A、PBP3和PBP4）的基因中的突变。因此，这些结果为理解耐药性的遗传基础以及高危克隆的传播和进化动态提供了有价值的信息。
