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Novobiocin binding to NalD induces the expression of the MexAB‐OprM pump in Pseudomonas aeruginosa
Author(s) -
Chen Weizhong,
Wang Dan,
Zhou Wenquan,
Sang Hong,
Liu Xichun,
Ge Zhiyun,
Zhang Jin,
Lan Lefu,
Yang CaiGuang,
Chen Hao
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13346
Subject(s) - biology , pseudomonas aeruginosa , novobiocin , repressor , efflux , tetr , multiple drug resistance , microbiology and biotechnology , genetics , antibiotics , bacteria , gene expression , gene
Summary NalD was reported to be the secondary repressor of the MexAB‐OprM multidrug efflux pump, the major system contributing to intrinsic multidrug resistance in Pseudomonas aeruginosa . Here, we show that novobiocin binds directly to NalD, which leads NalD to dissociate from the DNA promoter, and thus de‐represses the expression of the MexAB‐OprM pump. In addition, we have solved the crystal structure of NalD at a resolution of 2.90 Å. The structural alignment of NalD to its homologue TtgR reveals that the residues N129 and H167 in NalD are involved in its novobiocin‐binding ability. We have confirmed the function of these two amino acids by EMSA and plate assay. The results presented here highlight the importance and diversity of regulatory mechanism in bacterial antibiotic resistance, and provide further insight for novel antimicrobial development.