Plos Genetics:中科院微生物所冯婕课题组揭示不动杆菌中新型固有

2017年2月2日，国际知名学术期刊《PLOS genetics》杂志在线发表了中国科学院微生物研究所冯婕课题组题为A new subclass of intrinsic aminoglycoside nucleotidyltransferases, ANT(3")-II, is horizontally transferred among Acinetobacter spp. by homologous recombination 的论文,微生物所助理研究员张刚是该论文的第一作者，冯婕为通讯作者。

不动杆菌的耐药性包括获得性耐药和固有耐药。固有耐药是细菌对某类抗生素的天然耐受，由固有耐药基因决定。固有耐药基因是指存在于某类细菌染色体上位置保守的与耐药相关的一类基因。固有耐药基因的发现可以为新药研制提供药物作用靶标，并且固有耐药基因可以被移动原件捕获而成为获得性耐药的来源。

针对固有耐药，冯婕课题组之前已在蜡样芽孢杆菌群和铜绿假单胞菌中分别发现了新型固有大环内酯磷酸转移酶[Environ Microbiol. 2015, 17(5):1560-73]和固有的氨基糖苷磷酸转移酶耐药基因[antimicrob Agents Chemother. 2016, 60(11): 6983-85]。

最近，冯婕课题组在人类重要病原细菌不动杆菌中又发现了新型的氨基糖苷腺苷转移酶ANT(3")-II(包括IIa, IIb, IIc)，该酶广泛分布在不动杆菌属中，包括临床常见的鲍曼不动杆菌(Acinetobacter baumanii, IIa)、皮特不动杆菌(Acinetobacter pittii, IIa)、吉伦伯不动杆菌(Acinetobacter gyllenbergii, IIc)、小不动杆菌(Acinetobacter parvus, IIc)和其它未确定名称的不动杆菌(Acinetobacter sp., IIb和IIc)。

系统进化分析显示ANT(3")-II与已知的ANT(3")-I进化关系最近，在进化树上形成了单独的两个分枝，已知的ANT(3")-I普遍位于革兰氏阴性菌的移动原件中，而ANT(3")-II只特异性存在于不动杆菌的染色体保守位置上，因此ANT(3")-II是一个新的氨基糖苷腺苷转移酶亚类。

进一步研究发现，ant(3")-II基因可以在不动杆菌中进行频繁的水平转移。例如鲍曼不动杆菌的ant(3")-IIa基因可以转移至琼氏不动杆菌(Acinetobacter junii)，并且这种水平转移是通过同源重组、而非移动原件介导的(图1)。对不动杆菌所含全部基因进行重组热点分析，发现ant(3")-II基因位于染色体的重组热点区(图2)，表明ant(3")-II基因在不动杆菌中频繁转移。这一发现首次表明固有耐药基因可以通过同源重组的方式在不动杆菌的不同种间进行传播。

原文链接：

A new subclass of intrinsic aminoglycoside nucleotidyltransferases, ANT(3")-II, is horizontally transferred among Acinetobacter spp. by homologous recombination

原文摘要：

The emergence and spread of antibiotic resistance among Acinetobacter spp. have been investigated extensively. Most studies focused on the multiple antibiotic resistance genes located on plasmids or genomic resistance islands. On the other hand, the mechanisms controlling intrinsic resistance are still not well understood. In this study, we identified the novel subclass of aminoglycoside nucleotidyltransferase ANT(3")-II in Acinetobacter spp., which comprised numerous variants distributed among three main clades. All members of this subclass can inactivate streptomycin and spectinomycin. The three ant(3")-II genes, encoding for the three ANT(3")-II clades, are widely distributed in the genus Acinetobacter and always located in the same conserved genomic region. According to their prevalence, these genes are intrinsic in Acinetobacter baumannii, Acinetobacter pittii, and Acinetobacter gyllenbergii. We also demonstrated that the ant(3")-II genes are located in a homologous recombination hotspot and were recurrently transferred among Acinetobacter species. In conclusion, our findings demonstrated a novel mechanism of natural resistance in Acinetobacter spp., identified a novel subclass of aminoglycoside nucleotidyltransferase and provided new insight into the evolutionary history of intrinsic resistance genes.

doi:10.1371/journal.pgen.1006602

作者：冯婕