Five decades of genome evolution in the globally distributed, extensively antibiotic-resistant Acinetobacter baumannii global clone 1.
Five decades of genome evolution in the globally distributed, extensively antibiotic-resistant Acinetobacter baumannii global clone 1.
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DOI：
10.1099/mgen.0.000052
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发表时间：
2016-02
影响因子：
3.9
通讯作者：
Hall R
中科院分区：
文献类型：
--
作者：
Holt K;Kenyon JJ;Hamidian M;Schultz MB;Pickard DJ;Dougan G;Hall R
大多数具有多重、广泛和泛抗生素耐药性的鲍曼不动杆菌菌株属于两个全球传播的克隆 GC1 和 GC2，这两个克隆于 20 世纪 70 年代首次被发现。在这里，我们通过分析 45 个全基因组序列（包括本研究中测序的 23 个）来研究 GC1 内的微进化和系统动力学。 GC1 最近的共同祖先出现在 1960 年左右，后来分化成两个系统发育不同的谱系。 20 世纪 70 年代，主要谱系通过水平基因转移事件获得了 AbaR 抗性岛，赋予了对旧抗生素的抗性。我们估计~5个SNP基因组- 1年- 1的突变率，并检测到GC1基因组内的广泛重组，以> 20倍的替代率将核苷酸多样性引入群体（重组引入的SNP与突变的比率为22）。重组事件在基因组中非随机分布，并在编码外表面分子（包括荚膜多糖、外核脂寡糖和外膜蛋白 CarO）的基因座内产生显着的多样性，并传播影响 gyrA 和 parC 基因的抗菌耐药性突变以及激活 ampC 基因的插入序列插入。两个 GC1 谱系都通过各种遗传机制积累了对新型抗生素的耐药性，包括获得质粒和转座子或染色体基因突变。我们的数据显示，GC1 已多样化为多个成功的广泛抗生素耐药亚克隆，这些亚克隆的表面结构有所不同。这对所有控制途径都具有重要意义，包括流行病学追踪、抗菌治疗和疫苗接种。
The majority of Acinetobacter baumannii isolates that are multiply, extensively and pan-antibiotic resistant belong to two globally disseminated clones, GC1 and GC2, that were first noticed in the 1970s. Here, we investigated microevolution and phylodynamics within GC1 via analysis of 45 whole-genome sequences, including 23 sequenced for this study. The most recent common ancestor of GC1 arose around 1960 and later diverged into two phylogenetically distinct lineages. In the 1970s, the main lineage acquired the AbaR resistance island, conferring resistance to older antibiotics, via a horizontal gene transfer event. We estimate a mutation rate of ∼5 SNPs genome− 1 year− 1 and detected extensive recombination within GC1 genomes, introducing nucleotide diversity into the population at >20 times the substitution rate (the ratio of SNPs introduced by recombination compared with mutation was 22). The recombination events were non-randomly distributed in the genome and created significant diversity within loci encoding outer surface molecules (including the capsular polysaccharide, the outer core lipooligosaccharide and the outer membrane protein CarO), and spread antimicrobial resistance-conferring mutations affecting the gyrA and parC genes and insertion sequence insertions activating the ampC gene. Both GC1 lineages accumulated resistance to newer antibiotics through various genetic mechanisms, including the acquisition of plasmids and transposons or mutations in chromosomal genes. Our data show that GC1 has diversified into multiple successful extensively antibiotic-resistant subclones that differ in their surface structures. This has important implications for all avenues of control, including epidemiological tracking, antimicrobial therapy and vaccination.