Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA
Antimicrob Agents Chemother. 2017 Oct 24;61(11). doi: 10.1128/AAC.01347-17. Print 2017 Nov.
causes acute and chronic bronchopulmonary infection in patients with chronic lung damage, of which cystic fibrosis (CF) patients are particularly vulnerable. The major threat posed by this organism is its high intrinsic antibiotic resistance. A typical treatment regimen involves a 6- to 12-month-long combination therapy of clarithromycin and amikacin, with cure rates below 50% and multiple side effects, especially due to amikacin. In the present work, we show that , a homologue of and with previously demonstrated effects on intrinsic antibiotic resistance, is strongly induced when exposed to clinically relevant antibiotics that target the ribosome: erythromycin, clarithromycin, amikacin, tetracycline, and spectinomycin. The deletion of results in sensitivity to all of the above-mentioned antibiotics. Further, we have defined and compared the regulon of with the closely related nontuberculous mycobacterium (NTM) to demonstrate the induction of a species-specific repertoire of genes. Finally, we show that one such gene, , is specifically induced in by and contributes to its higher levels of intrinsic amikacin resistance. This species-specific pattern of gene induction might account for the differences in drug susceptibilities to other antibiotics and between different mycobacterial species.
在慢性肺部损伤患者中引起急性和慢性支气管肺部感染，其中囊性纤维化（CF）患者特别容易受到感染。该生物体的主要威胁是其固有抗生素耐药性高。典型的治疗方案包括克拉霉素和阿米卡星联合治疗 6-12 个月，治愈率低于 50%，并且有多种副作用，尤其是由于阿米卡星引起的副作用。在本工作中，我们表明，与先前证明对固有抗生素耐药性有影响的 和 同源物，当暴露于针对核糖体的临床相关抗生素（如红霉素、克拉霉素、阿米卡星、四环素和大观霉素）时，会被强烈诱导。缺失 会导致对上述所有抗生素的敏感性。此外，我们已经定义并比较了与密切相关的非结核分枝杆菌（NTM）的 调控组，以证明诱导出了特定于物种的基因组合。最后，我们表明，其中一个基因 ，在 中被 和特异性诱导，并有助于其对阿米卡星固有耐药性的提高。这种特定于物种的基因诱导模式可能解释了对其他抗生素的药物敏感性差异以及不同分枝杆菌物种之间的差异。
