Expansion and Evolution of a Virulent, Extensively Drug-Resistant (Polymyxin B-Resistant), QnrS1-, CTX-M-2-, and KPC-2-Producing Klebsiella pneumoniae ST11 International High-Risk Clone
Expansion and Evolution of a Virulent, Extensively Drug-Resistant (Polymyxin B-Resistant), QnrS1-, CTX-M-2-, and KPC-2-Producing Klebsiella pneumoniae ST11 International High-Risk Clone
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DOI：
10.1128/jcm.00088-14
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发表时间：
2014-07-01
影响因子：
9.4
通讯作者：
Costa Darini, Ana Lucia
中科院分区：
文献类型：
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作者：
Andrade, Leonardo Neves;Vitali, Lucia;Costa Darini, Ana Lucia
在这项研究中，我们报告了一种多重耐药肺炎克雷伯菌克隆的早期扩增、进化和特征，该克隆从巴西一家三级保健大学医院的住院患者中分离出来的频率越来越高。对2012年12月至2013年2月分离的7株碳青霉烯-喹诺酮类耐药和多粘菌素b敏感或耐药肺炎克雷伯菌进行了调查。采用PCR、测序和限制性片段长度多态性（RFLP）研究β -内酰胺酶和质粒介导的喹诺酮类药物耐药（PMQR）编码基因及其遗传环境。克隆亲缘关系通过xbai -脉冲场凝胶电泳（PFGE）、多位点序列分型（MLST）和系统发育类群鉴定确定。质粒分析包括基于pcr的复制子分型（PBRT）、S1-PFGE产物的杂交、质粒MLST和偶联实验。采用PCR方法搜索10个毒力因子编码基因（ureA、fimH、kfuBC、uge、wabG、magA、mrkD、allS、rmpA、cf29a）评估毒力潜力，并通过表型检测分析高粘滞表型。发现了一个多重耐药和广泛耐药的肺炎克雷伯菌ST11-KpI克隆携带IncFIIk-Tn4401a-bla（KPC-2）、qnrS1和bla（CTX-M-2）的遗传背景。此外，三个分离株对多粘菌素B表现出高耐药性（mic = 32、32和128 mg/l），并表现出黏液和高黏液粘性表型。这些细菌还携带尿素、fimH、uge、wabG和mrkD，它们编码与结合、生物膜形成、定植和逃避吞噬能力相关的毒力因子。我们的研究描述了重要的共耐药和毒力因素在肺炎克雷伯菌ST11国际高危克隆中的关联，这使得该病原体在感染中成功，并指出这种多重耐药和毒力克隆的快速扩展和进化，导致巴西一家医院的普遍耐药表型和持久性细菌。
In this study, we report the early expansion, evolution, and characterization of a multiresistant Klebsiella pneumoniae clone that was isolated with increasing frequency from inpatients in a tertiary-care university hospital in Brazil. Seven carbapenem-and quinolone-resistant and polymyxin B-susceptible or -resistant K. pneumoniae isolates isolated between December 2012 and February 2013 were investigated. Beta-lactamase-and plasmid-mediated quinolone resistance (PMQR)-encoding genes and the genetic environment were investigated using PCR, sequencing, and restriction fragment length polymorphism ( RFLP). Clonal relatedness was established using XbaI-pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and phylogenetic group characterization. Plasmid analyses included PCR-based replicon typing (PBRT) and hybridization of the S1-PFGE product, plasmid MLST, and conjugation experiments. Virulence potential was assessed by PCR by searching for 10 virulence factor-encoding genes (ureA, fimH, kfuBC, uge, wabG, magA, mrkD, allS, rmpA, and cf29a) and by phenotypic tests to analyze the hypermucoviscous phenotype. The genetic context of a multidrug-resistant and extensively drug-resistant K. pneumoniae ST11-KpI clone harboring IncFIIk-Tn4401a-bla(KPC-2), qnrS1, and bla(CTX-M-2) was found. Moreover, three isolates displayed high resistance to polymyxin B (MICs = 32, 32, and 128 mg/liter) as well as mucous and hypermucoviscous phenotypes. These bacteria also harbored ureA, fimH, uge, wabG, and mrkD, which code for virulence factors associated with binding, biofilm formation, and the ability to colonize and escape from phagocytosis. Our study describes the association of important coresistance and virulence factors in the K. pneumoniae ST11 international high-risk clone, which makes this pathogen successful at infections and points to the quick expansion and evolution of this multiresistant and virulent clone, leading to a pandrug-resistant phenotype and persistent bacteria in a Brazilian hospital.