Triclosan Can Select for an AdeIJK-Overexpressing Mutant of Acinetobacter baumannii ATCC 17978 That Displays Reduced Susceptibility to Multiple Antibiotics
Triclosan Can Select for an AdeIJK-Overexpressing Mutant of Acinetobacter baumannii ATCC 17978 That Displays Reduced Susceptibility to Multiple Antibiotics
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DOI：
10.1128/aac.03074-14
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发表时间：
2014-11-01
影响因子：
4.9
通讯作者：
Kumar, Ayush
中科院分区：
文献类型：
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作者：
Fernando, Dinesh M.;Xu, Wayne;Kumar, Ayush
为了确定三氯生是否可以选择鲍曼不动杆菌ATCC 17978的突变体，这些突变体对抗生素的敏感性降低，我们分离了一个三氯生抗性突变体，A。鲍曼不动杆菌AB 042，通过连续传代。鲍曼不动杆菌ATCC 17978在补充有三氯生的生长培养基中。采用2倍连续稀释法分析AB 042的抗菌药物敏感性。使用定量逆转录酶（qRT）PCR分析了五种不同的抗性结瘤分裂（RND）泵编码基因（adeB、adeG、adeJ、A1S_2818和A1S_3217）、两种外膜孔蛋白编码基因（carO和oprD）以及MATE家族泵编码基因abeM的表达。A.鲍曼不动杆菌AB 042显示出对多种抗生素的高耐药性，所述抗生素包括哌拉西林-他唑巴坦、多西环素、阿替沙星、头孢曲松、头孢吡肟、美罗培南、多利培南、厄他培南、环丙沙星、氨曲南、替加环素和甲氧苄啶-磺胺甲恶唑，以及三氯生。A.鲍曼不动杆菌AB 042揭示了fabI（三氯生的靶酶编码基因）中的（116）G -> V突变。外排泵的表达分析显示AdeIJK泵的过表达，并且编码AdeIJK操纵子的阻遏物的基因亚丁的测序揭示了73-bp缺失，这将导致翻译的过早终止，导致无活性的截短的亚丁蛋白。这项工作表明，三氯生可以选择突变的A。这些鲍曼不动杆菌除了对三氯生耐药性外，还表现出对来自化学上不同类别的多种抗生素的敏感性降低。这种多药耐药性可以通过AdeIJK外排泵的过表达来解释。
In order to determine if triclosan can select for mutants of Acinetobacter baumannii ATCC 17978 that display reduced susceptibilities to antibiotics, we isolated a triclosan-resistant mutant, A. baumannii AB042, by serial passaging of A. baumannii ATCC 17978 in growth medium supplemented with triclosan. The antimicrobial susceptibility of AB042 was analyzed by the 2-fold serial dilution method. Expression of five different resistance-nodulation-division (RND) pump-encoding genes (adeB, adeG, adeJ, A1S_2818, and A1S_3217), two outer membrane porin-encoding genes (carO and oprD), and the MATE family pump-encoding gene abeM was analyzed using quantitative reverse transcriptase (qRT) PCR. A. baumannii AB042 exhibited elevated resistance to multiple antibiotics, including piperacillin-tazobactam, doxycycline, moxifloxacin, ceftriaxone, cefepime, meropenem, doripenem, ertapenem, ciprofloxacin, aztreonam, tigecycline, and trimethoprim-sulfamethoxazole, in addition to triclosan. Genome sequencing of A. baumannii AB042 revealed a (116)G -> V mutation in fabI, the gene encoding the target enzyme for triclosan. Expression analysis of efflux pumps showed overexpression of the AdeIJK pump, and sequencing of adeN, the gene that encodes the repressor of the adeIJK operon, revealed a 73-bp deletion which would cause a premature termination of translation, resulting in an inactive truncated AdeN protein. This work shows that triclosan can select for mutants of A. baumannii that display reduced susceptibilities to multiple antibiotics from chemically distinct classes in addition to triclosan resistance. This multidrug resistance can be explained by the overexpression of the AdeIJK efflux pump.