Silent transmission of an IS1294b-deactivated mcr-1 gene with inducible colistin resistance
Silent transmission of an IS1294b-deactivated mcr-1 gene with inducible colistin resistance
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IS1294b 失活的 mcr-1 基因的无声传播具有诱导型粘菌素抗性
DOI：
10.1016/j.ijantimicag.2018.01.004
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发表时间：
2018
影响因子：
10.8
通讯作者：
Lanjuan Li
中科院分区：
文献类型：
--
作者：
Kai Zhou;Qixia Luo;Qin Wang;Chen Huang;Haifeng Lu;John W. A.Rossen;Yonghong Xiao;Lanjuan Li
移动粘菌素耐药性 mcr-1 的全球传播尤其值得关注，因为粘菌素是治疗由碳青霉烯类耐药革兰氏阴性菌引起的严重感染的最后手段抗生素之一。在这项研究中，对氟喹诺酮耐药且粘菌素敏感的尿路致病性大肠杆菌分离株 (ECO3347) 中的 mcr-1 失活形式进行了表征。 Themcr-1 基因通过插入侧翼有两个四聚体 (GTTC) 的 1.7 kb IS1294b 元件而失活，并且位于 62 kb pHNSHP45 样质粒 (p3347-mcr-1) 上。使用单步和多步选择在ECO3347中体外诱导粘菌素抗性。仅在增加粘菌素浓度 (2–8mg/L) 的连续传代选择后，ECO3347 才获得粘菌素抗性 (MIC = 16–32mg/L)。失活的 mcr-1 通过 IS1294b 的丢失而重新激活，在大多数粘菌素抗性突变体中没有任何残留。此外，在一个粘菌素抗性突变体中检测到 PmrA CheY 同源受体结构域中的一种新氨基酸变体 (Leu105Pro)。携带重新激活的mcr-1基因的质粒p3347-mcr-1+可转移至大肠杆菌。 coliJ53 受体具有高接合率（每个受体细胞约 10-1 个细胞）。转接合子表现出与 J53 相同的生长状态，表明在获得 p3347-mcr-1+ 后缺乏适应性成本。这些结果表明，在类似 pHNSHP45 的流行性质粒的帮助下，被破坏的 mcr-1 基因具有广泛沉默传播的潜力。诱导性粘菌素耐药性可能会影响临床治疗和感染控制的成功。持续监测 mcr-1 对于了解和应对其不同形式的传播至关重要。
Global dissemination of the mobile colistin resistancemcr-1is of particular concern as colistin is one of the last-resort antibiotics for the treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria. In this study, an inactive form ofmcr-1in a fluoroquinolone-resistant and colistin-susceptible uropathogenicEscherichia coliisolate (ECO3347) was characterised. Themcr-1gene was deactivated by insertion of a 1.7-kb IS1294belement flanked by two tetramers (GTTC) and located on a 62-kb pHNSHP45-like plasmid (p3347-mcr-1). Single-step and multistep selections were used to induce colistin resistance in vitro in ECO3347. ECO3347 acquired colistin resistance (MIC = 16–32 mg/L) only after a serial passage selection with increasing concentrations of colistin (2–8 mg/L). Deactivatedmcr-1was re-activated by loss of IS1294bwithout any remnants in most colistin-resistant mutants. In addition, a novel amino acid variant (Leu105Pro) in the CheY homologous receiver domain of PmrA was detected in one colistin-resistant mutant. Plasmid p3347-mcr-1+carrying the re-activatedmcr-1gene is transferrable toE. coliJ53 recipient with a high conjugation rate (ca. 10–1cells per recipient cell). Transconjugants showed an identical growth status to J53, suggesting lack of a fitness cost after acquiring p3347-mcr-1+. These results highlight that the disruptedmcr-1gene has the potential for wide silent dissemination with the help of pHNSHP45-like epidemic plasmids. Inducible colistin resistance may likely compromise the success of clinical treatment and infection control. Continuous monitoring ofmcr-1is imperative for understanding and tackling its dissemination in different forms.