PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa.
PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa.
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PA3297 抵消阿奇霉素对铜绿假单胞菌的抗菌作用
DOI：
10.3389/fmicb.2016.00317
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发表时间：
2016
影响因子：
5.2
通讯作者：
Wu W
中科院分区：
文献类型：
--
作者：
Tan H;Zhang L;Weng Y;Chen R;Zhu F;Jin Y;Cheng Z;Jin S;Wu W
铜绿假单胞菌可引起人类急性和慢性感染。它对抗生素的耐药性日益增加，需要比现有策略更有效的替代治疗。替代方案之一是非常规使用常规抗生素，其中大环内酯类抗生素阿奇霉素（AZM）提供了一个范例。AZM治疗与慢性铜绿假单胞菌感染的囊性纤维化患者呼吸功能的小幅但持续改善有关。除了免疫调节活性外，AZM还抑制与毒力、群体感应、生物膜形成和运动有关的细菌基因，这些基因都是由于核糖体的停滞和细胞tRNA池的耗尽而产生的。然而，铜绿假单胞菌如何响应和抵消AZM的影响仍然是难以捉摸的。在这里，我们发现PA3297（一种编码DEAH-box解旋酶的基因）的缺失会加剧azm介导的细菌杀伤，抑制pyocyanin的产生和蜂群运动，以及对过氧化氢的超敏感。我们证明了PA3297的表达是由AZM和核糖体相互作用诱导的。重要的是，PA3297突变导致AZM存在时未加工的23S-5S rRNA水平升高，这可能导致对AZM介导效应的易感性增加。我们的研究结果揭示了一种细菌反应在抵消AZM的有害影响。
Pseudomonas aeruginosa causes acute and chronic infections in human. Its increasing resistance to antibiotics requires alternative treatments that are more effective than available strategies. Among the alternatives is the unconventional usage of conventional antibiotics, of which the macrolide antibiotic azithromycin (AZM) provides a paradigmatic example. AZM therapy is associated with a small but consistent improvement in respiratory function of cystic fibrosis patients suffering from chronic P. aeruginosa infection. Besides immunomodulating activities, AZM represses bacterial genes involved in virulence, quorum sensing, biofilm formation, and motility, all of which are due to stalling of ribosome and depletion of cellular tRNA pool. However, how P. aeruginosa responds to and counteracts the effects of AZM remain elusive. Here, we found that deficiency of PA3297, a gene encoding a DEAH-box helicase, intensified AZM-mediated bacterial killing, suppression of pyocyanin production and swarming motility, and hypersusceptibility to hydrogen peroxide. We demonstrated that expression of PA3297 is induced by the interaction between AZM and ribosome. Importantly, mutation of PA3297 resulted in elevated levels of unprocessed 23S-5S rRNA in the presence of AZM, which might lead to increased susceptibility to AZM-mediated effects. Our results revealed one of the bacterial responses in counteracting the detrimental effects of AZM.