Resistance-Nodulation-Division Efflux Pump, LexABC, Contributes to Self-Resistance of the Phenazine Di-N-Oxide Natural Product Myxin in Lysobacter antibioticus.
Resistance-Nodulation-Division Efflux Pump, LexABC, Contributes to Self-Resistance of the Phenazine Di-N-Oxide Natural Product Myxin in Lysobacter antibioticus.
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抗性结瘤分裂外排泵 LexABC 有助于溶杆菌中吩嗪二氮氧化物天然产物 Myxin 的自我抵抗
DOI：
10.3389/fmicb.2021.618513
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发表时间：
2021
影响因子：
5.2
通讯作者：
Liu F
中科院分区：
文献类型：
--
作者：
Zhao Y;Liu J;Jiang T;Hou R;Xu G;Xu H;Liu F
抗生素生产微生物已经发展了几种自我抗性机制来保护它们免受自毒作用。属于耐药-结瘤-分裂（RND）超家族的转运蛋白通常在革兰氏阴性菌中赋予多药耐药性。吩嗪是杂环、含氮和氧化还原活性化合物，具有多种活性。我们以前确定了六吩嗪溶杆菌OH 13，土壤细菌新兴作为一个潜在的生物防治剂。在这些吩嗪类化合物中，二-N-氧化物吩嗪类化合物粘菌素对多种微生物表现出有效的活性。在这项研究中，我们确定了一个新的RND外排泵基因簇，命名为lexABC，它位于远离基因组中的粘菌素生物合成基因簇。我们发现了一个推定的LysR型转录调节因子编码基因lexR，这是相邻的lexABC。lexABC或lexR基因的缺失导致菌株对粘菌素的敏感性显着增加和损失的粘菌素生产。结果表明LexABC泵赋予对粘菌素的抗性。在这些突变体中以较低浓度产生的粘菌素通过脱氧和O-甲基化而衍生化。此外，我们发现，取消与LaPhzB，这是一个必需的基因在粘菌素生物合成的缺失，导致lexABC的显着下调的粘菌素。而外源添加粘菌素可有效诱导lexABC基因的表达。此外，lexR突变也导致lexABC表达降低，这表明LexR可能正调控lexABC的表达。我们的研究结果揭示了L.协调调节途径以保护自身免受自毒性。
Antibiotic-producing microorganisms have developed several self-resistance mechanisms to protect them from autotoxicity. Transporters belonging to the resistance- nodulation-division (RND) superfamily commonly confer multidrug resistance in Gram-negative bacteria. Phenazines are heterocyclic, nitrogen-containing and redox-active compounds that exhibit diverse activities. We previously identified six phenazines from Lysobacter antibioticus OH13, a soil bacterium emerging as a potential biocontrol agent. Among these phenazines, myxin, a di-N-oxide phenazine, exhibited potent activity against a variety of microorganisms. In this study, we identified a novel RND efflux pump gene cluster, designated lexABC, which is located far away in the genome from the myxin biosynthesis gene cluster. We found a putative LysR-type transcriptional regulator encoding gene lexR, which was adjacent to lexABC. Deletion of lexABC or lexR gene resulted in significant increasing susceptibility of strains to myxin and loss of myxin production. The results demonstrated that LexABC pump conferred resistance against myxin. The myxin produced at lower concentrations in these mutants was derivatized by deoxidation and O-methylation. Furthermore, we found that the abolishment of myxin with deletion of LaPhzB, which is an essential gene in myxin biosynthesis, resulted in significant downregulation of the lexABC. However, exogenous supplementation with myxin to LaPhzB mutant could efficiently induce the expression of lexABC genes. Moreover, lexR mutation also led to decreased expression of lexABC, which indicates that LexR potentially positively modulated the expression of lexABC. Our findings reveal a resistance mechanism against myxin of L. antibioticus, which coordinates regulatory pathways to protect itself from autotoxicity.
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