广泛耐药的 GC1 鲍曼不动杆菌 MRSN 56 全基因组揭示了一种新型氟喹诺酮类耐药途径。
Complete genome of the extensively antibiotic-resistant GC1 Acinetobacter baumannii isolate MRSN 56 reveals a novel route to fluoroquinolone resistance.
机构信息
School of Life and Environmental Sciences, The University of Sydney, Sydney, Australia.
Multidrug Resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
出版信息
J Antimicrob Chemother. 2022 Jun 29;77(7):1851-1855. doi: 10.1093/jac/dkac115.
OBJECTIVES
To examine the causes of antibiotic resistance in the extensively resistant global clone 1 (GC1) Acinetobacter baumannii isolate MRSN 56 recovered at a US military treatment facility.
METHODS
MRSN 56 was sequenced using MinION (Oxford Nanopore) and the reads combined with available Illumina MiSeq data using Unicycler. Acquired resistance genes were identified using ABRicate and their environment examined. ISAba1 and ISAba125 copies were located.
RESULTS
MRSN 56 is ST1IP:ST231Ox:KL1:OCL1 and the complete genome includes four small plasmids, none of which carry resistance genes. The acquired resistance genes were found at four locations in the chromosome in addition to AbaR28 (aphA1, aacC1, aadA1, sul1) in comM. Tn2006 (oxa23, carbapenem resistance) was both in AbaR4 and alone elsewhere. Two copies of Tn7 (dfrA1, sat, aadA1) were identified. One was associated with a 22 852 bp adjacent segment [tetA(B), sul2] derived from the AbGRI1 island, and this novel configuration was designated Tn7+. Tn7+ was incorporated in the position preferred by Tn7, downstream of glmS, by transposition using a sequence in AbGRI1 resembling the Tn7 terminal inverted repeats. Tn7 was found at a secondary site. Fluoroquinolone resistance appears to involve a mutation in gyrA combined with inactivation by ISAba1 of the marR gene in the mar operon and constitutive expression of marA from the promoter internal to ISAba1.
CONCLUSIONS
MRSN 56 represents a new sublineage of GC1 lineage 1 with novel features that had not been detected previously. The involvement of the mar operon in fluoroquinolone resistance has not been noted previously.
目的
研究在美国军事治疗机构回收的广泛耐药全球克隆 1（GC1）鲍曼不动杆菌 MRSN 56 株抗生素耐药的原因。
方法
使用 MinION（Oxford Nanopore）对 MRSN 56 进行测序，并使用 Unicycler 将读取结果与现有的 Illumina MiSeq 数据结合。使用 ABRicate 识别获得的耐药基因，并检查其环境。定位 ISAba1 和 ISAba125 拷贝。
结果
MRSN 56 是 ST1IP：ST231Ox：KL1：OCL1，完整基因组包括四个小质粒，其中没有一个携带耐药基因。除了 comM 中的 AbaR28（aphA1、aacC1、aadA1、sul1）外，还在染色体的四个位置发现了获得的耐药基因。Tn2006（oxa23、碳青霉烯类耐药）同时存在于 AbaR4 和其他地方。鉴定出两个 Tn7（dfrA1、sat、aadA1）拷贝。一个与源自 AbGRI1 岛的 22852bp 相邻片段 [tetA(B)、sul2]相关，这种新构型被指定为 Tn7+。Tn7+通过使用类似于 Tn7 末端反向重复的 AbGRI1 中的序列在 glmS 下游转位，整合到 Tn7 偏好的位置。Tn7 位于次要位置。氟喹诺酮类耐药似乎涉及 gyrA 突变，以及 mar 操纵子中的 marR 基因被 ISAba1 失活，以及 ISAba1 内部启动子的 marA 组成型表达。
结论
MRSN 56 代表了具有先前未检测到的新特征的 GC1 谱系 1 的一个新亚系。mar 操纵子在氟喹诺酮类耐药中的参与以前没有被注意到。
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