Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant Enterobacter cloacae Complex Clones ST171 and ST78.
Genomic and Geographic Context for the Evolution of High-Risk Carbapenem-Resistant Enterobacter cloacae Complex Clones ST171 and ST78.
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DOI：
10.1128/mbio.00542-18
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发表时间：
2018-05-29
期刊：
影响因子：
6.4
通讯作者：
Uhlemann AC
中科院分区：
文献类型：
--
作者：
Gomez-Simmonds A;Annavajhala MK;Wang Z;Macesic N;Hu Y;Giddins MJ;O'Malley A;Toussaint NC;Whittier S;Torres VJ;Uhlemann AC
最近的报告已经确定了碳青霉烯类耐药阴沟肠杆菌复合体（CREC）的威胁不断升级。在这里，我们证明，CREC已演变为一个高度耐药，而不是高毒力的医院病原体。应用基因组学和贝叶斯系统发育分析7年收集的CREC分离株从北方曼哈顿医院系统和一个大的公开的，地理上不同的基因组，我们证明了一个单一的克隆，ST 171的克隆传播。我们估计，流行性ST 171的两个主要分支在1962年之前分化，随后从美国东北部平行传播到大西洋中部和中西部，并展示了与国际网站的联系。在20世纪80年代中期，这两个分支获得碳青霉烯和氟喹诺酮耐药决定因素之前，这些药物被广泛使用，这表明抗生素的压力大大促进了其传播。尽管具有独特的移动的库，但ST 171分离株在体外显示出降低的毒力。虽然第二个克隆ST 78在很大程度上促成了CREC的出现，但它包含了多种携带碳青霉烯酶的质粒，包括一种潜在的高传递性IncN质粒，也存在于其他序列类型中。CREC不是增强毒力，而是表现出对医院环境的谱系特异性、多因素适应，以及获得和传播碳青霉烯耐药基因的独特潜力。这些发现表明，需要进行强有力的监测工作，关注高风险CREC克隆在当地和国际传播的可能性。耐碳青霉烯类阴沟肠杆菌复合体（CREC）已成为一种强大的医院病原体。虽然质粒编码的碳青霉烯酶的零星获得被认为是CREC的主要驱动因素，但ST 171和ST 78克隆表现出流行潜力。然而，由于缺乏可靠的基因组参考和严格的统计分析，在成功的CREC的系统发育背景和进化途径方面留下了许多知识空白。我们重建最近的ST 171和ST 78的演变代表了一个重要的除了目前的了解CREC和其传播的方向性从美国东部到美国中西部的北方与国际收藏的联系。我们的研究结果表明，阴沟肠杆菌获得和传播跨类抗生素耐药性而不是毒力决定因素的显着能力，加上其在抗生素压力条件下的适应能力，可能导致CREC的广泛传播。
Recent reports have established the escalating threat of carbapenem-resistant Enterobacter cloacae complex (CREC). Here, we demonstrate that CREC has evolved as a highly antibiotic-resistant rather than highly virulent nosocomial pathogen. Applying genomics and Bayesian phylogenetic analyses to a 7-year collection of CREC isolates from a northern Manhattan hospital system and to a large set of publicly available, geographically diverse genomes, we demonstrate clonal spread of a single clone, ST171. We estimate that two major clades of epidemic ST171 diverged prior to 1962, subsequently spreading in parallel from the Northeastern to the Mid-Atlantic and Midwestern United States and demonstrating links to international sites. Acquisition of carbapenem and fluoroquinolone resistance determinants by both clades preceded widespread use of these drugs in the mid-1980s, suggesting that antibiotic pressure contributed substantially to its spread. Despite a unique mobile repertoire, ST171 isolates showed decreased virulence in vitro. While a second clone, ST78, substantially contributed to the emergence of CREC, it encompasses diverse carbapenemase-harboring plasmids, including a potentially hypertransmissible IncN plasmid, also present in other sequence types. Rather than heightened virulence, CREC demonstrates lineage-specific, multifactorial adaptations to nosocomial environments coupled with a unique potential to acquire and disseminate carbapenem resistance genes. These findings indicate a need for robust surveillance efforts that are attentive to the potential for local and international spread of high-risk CREC clones. Carbapenem-resistant Enterobacter cloacae complex (CREC) has emerged as a formidable nosocomial pathogen. While sporadic acquisition of plasmid-encoded carbapenemases has been implicated as a major driver of CREC, ST171 and ST78 clones demonstrate epidemic potential. However, a lack of reliable genomic references and rigorous statistical analyses has left many gaps in knowledge regarding the phylogenetic context and evolutionary pathways of successful CREC. Our reconstruction of recent ST171 and ST78 evolution represents a significant addition to current understanding of CREC and the directionality of its spread from the Eastern United States to the northern Midwestern United States with links to international collections. Our results indicate that the remarkable ability of E. cloacae to acquire and disseminate cross-class antibiotic resistance rather than virulence determinants, coupled with its ability to adapt under conditions of antibiotic pressure, likely led to the wide dissemination of CREC.