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LexR Positively Regulates the LexABC Efflux Pump Involved in Self-Resistance to the Antimicrobial Di-N-Oxide Phenazine in Lysobacter antibioticus

文献类型： 外文期刊

作者： Zhao, Yangyang 1 ; Xu, Gaoge 1 ; Xu, Zhizhou 1 ; Guo, Baodian 1 ; Liu, Fengquan 1 ;

作者机构： 1.Jiangsu Acad Agr Sci, Inst Plant Protect, Jiangsu Key Lab Food Qual & Safety, State Key Lab Cultivat Base,Minist Sci & Technol, Nanjing, Peoples R China

2.Hainan Univ, Sch Plant Protect, Key Lab Green Prevent & Control Trop Plant Dis & P, Minist Educ, Haikou, Peoples R China

3.Nanjing Agr Univ, Coll Plant Protect, Key Lab Integrated Management Crop Dis & Pests, Nanjing, Peoples R China

关键词： myxin; phenazine; Lysobacter antibioticus; self-resistance; efflux pump; LysR family regulator

期刊名称：MICROBIOLOGY SPECTRUM （ 影响因子：3.7； 五年影响因子：5.9 ）

ISSN： 2165-0497

年卷期： 2023 年 11 卷 3 期

页码：

收录情况： SCI

摘要： Antibiotic-producing bacteria exhibit various sophisticated mechanisms for self-protection against their own secondary metabolites. RND efflux pumps that eliminate antibiotics from cells are ubiquitous in Gram-negative bacteria. Myxin, a di-N-oxide phenazine isolated from the soil bacterium Lysobacter antibioticus, exhibits potent activity against various microorganisms and has the potential to be developed as an agrochemical. Antibiotic-producing microorganisms have developed self-resistance mechanisms to protect themselves from autotoxicity. Antibiotic efflux is vital for such protection. Recently, we identified a resistance-nodulation-division (RND) efflux pump, LexABC, involved in self-resistance against myxin in L. antibioticus. Expression of its genes, lexABC, was induced by myxin and was positively regulated by the LysR family transcriptional regulator LexR. The molecular mechanisms, however, have not been clear. Here, LexR was found to bind to the lexABC promoter region to directly regulate expression. Moreover, myxin enhanced this binding. Molecular docking and surface plasmon resonance analysis showed that myxin bound LexR with valine and lysine residues at positions 146 (V146) and 195 (K195), respectively. Furthermore, mutation of K195 in vivo led to downregulation of the gene lexA. These results indicated that LexR sensed and bound with myxin, thereby directly activating the expression of the LexABC efflux pump and increasing L. antibioticus resistance against myxin.IMPORTANCE Antibiotic-producing bacteria exhibit various sophisticated mechanisms for self-protection against their own secondary metabolites. RND efflux pumps that eliminate antibiotics from cells are ubiquitous in Gram-negative bacteria. Myxin is a heterocyclic N-oxide phenazine with potent antimicrobial and antitumor activities produced by the soil bacterium L. antibioticus. The RND pump LexABC contributes to the self-resistance of L. antibioticus against myxin. Herein, we report a mechanism involving the LysR family regulator LexR that binds to myxin and directly activates the LexABC pump. Further study on self-resistance mechanisms could help the investigation of strategies to deal with increasing bacterial antibiotic resistance and enable the discovery of novel natural products with resistance genes as selective markers.

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