Deletion of TnAbaR23 Results in both Expected and Unexpected Antibiogram Changes in a Multidrug-Resistant Acinetobacter baumannii Strain
Deletion of TnAbaR23 Results in both Expected and Unexpected Antibiogram Changes in a Multidrug-Resistant Acinetobacter baumannii Strain
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TnAbaR23 的删除导致多重耐药鲍曼不动杆菌菌株中预期和意外的抗菌谱变化
DOI：
10.1128/aac.05334-11
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发表时间：
2012-04-01
影响因子：
4.9
通讯作者：
Rajakumar, Kumar
中科院分区：
文献类型：
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作者：
Kocher, Mandira;Crosatti, Marialuisa;Rajakumar, Kumar
自2006年发现鲍曼不动杆菌菌株AYE AbaR 1耐药岛以来，在该物种的许多成员中报告了类似的元件。由于AbaR 1与Tn 7关系较远，我们将其重命名为TnAbaR 1。已知TnAbaR转座子携带多种抗生素耐药性和外排相关基因，尽管没有一个被整体实验研究。我们删除了A中的TnAbaR转座子。鲍曼不动杆菌A424，我们将其命名为TnAbaR 23，并表征了独立缺失突变体DCO 163和DCO 174。菌株DCO 174的NotI脉冲场凝胶电泳（PFGE）图谱与单独TnAbaR 23的靶向缺失一致，但菌株DCO 163显然含有第二个大的基因组缺失。然而，针对52个TnAbaR和/或抗性相关基因座的“消减扩增”对两种突变体产生了相同的结果，并突出显示了相对于菌株A424丢失的基因。PCR定位和基因组测序揭示了TnAbaR 23的整个48.3-kb序列。与TnAbaR 23携带两个拷贝的sul 1一致，这两种突变体对磺胺甲恶唑的敏感性显著增加。相比之下，tetAR（A）的缺失仅导致四环素敏感性的微小和可变增加。尽管没有表现出生长障碍，但菌株DCO 163比菌株DCO 174对10种抗生素中的9种更敏感，这与敏感性的突变变异相关，表明未定义的耐药相关功能受损。值得注意的是，尽管所有三种菌株共享相同的gyrA和parC序列，但DCO 174的环丙沙星MIC是DCO 163和A424的>8倍，表明TnAbaR 23在促进对环丙沙星的敏感性方面可能具有矛盾的作用。这项研究强调了实验审查的重要性，并挑战了单从基因型就可以可靠预测耐药表型的假设。
Since the 2006 discovery of the Acinetobacter baumannii strain AYE AbaR1 resistance island, similar elements have been reported in numerous members of this species. As AbaR1 is distantly related to Tn7, we have renamed it TnAbaR1. TnAbaR transposons are known to carry multiple antibiotic resistance- and efflux-associated genes, although none have been experimentally studied en bloc. We deleted the TnAbaR transposon in A. baumannii A424, which we have designated TnAbaR23, and characterized independent deletion mutants DCO163 and DCO174. The NotI pulsed-field gel electrophoresis (PFGE) profile of strain DCO174 was consistent with targeted deletion of TnAbaR23 alone, but strain DCO163 apparently harbored a second large genomic deletion. Nevertheless, "subtractive amplification" targeting 52 TnAbaR and/or resistance-associated loci yielded identical results for both mutants and highlighted genes lost relative to strain A424. PCR mapping and genome sequencing revealed the entire 48.3-kb sequence of TnAbaR23. Consistent with TnAbaR23 carrying two copies of sul1, both mutants exhibited markedly increased susceptibility to sulfamethoxazole. In contrast, loss of tetAR(A) resulted in only a minor and variable increase in tetracycline susceptibility. Despite not exhibiting a growth handicap, strain DCO163 was more susceptible than strain DCO174 to 9 of 10 antibiotics associated with mutant-to-mutant variation in susceptibility, suggesting impairment of an undefined resistance-associated function. Remarkably, despite all three strains sharing identical gyrA and parC sequences, the ciprofloxacin MIC of DCO174 was >8-fold that of DCO163 and A424, suggesting a possible paradoxical role for TnAbaR23 in promoting sensitivity to ciprofloxacin. This study highlights the importance of experimental scrutiny and challenges the assumption that resistance phenotypes can reliably be predicted from genotypes alone.