Conformation control of the histidine kinase BceS ofBacillus subtilisby its cognate ABC-transporter facilitates need-based activation of antibiotic resistance

被引:23
作者
Koh, Alan [1 ,2 ]
Gibbon, Marjorie J. [1 ,2 ]
van der Kamp, Marc W. [3 ]
Pudney, Christopher R. [1 ]
Gebhard, Susanne [1 ,2 ]
机构
[1] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England
[2] Univ Bath, Milner Ctr Evolut, Bath, Avon, England
[3] Univ Bristol, Sch Biochem, Bristol, Avon, England
基金
英国生物技术与生命科学研究理事会;
关键词
antimicrobial peptide; cell envelope stress; flux-sensing; signal transduction; DISULFIDE CROSS-LINKING; ESCHERICHIA-COLI; ANTIMICROBIAL PEPTIDES; DETOXIFICATION MODULES; BACITRACIN RESISTANCE; MECHANISM; IDENTIFICATION; TRANSDUCTION; PREDICTION; DCTA/DCUS;
D O I
10.1111/mmi.14607
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bacteria closely control gene expression to ensure optimal physiological responses to their environment. Such careful gene expression can minimize the fitness cost associated with antibiotic resistance. We previously described a novel regulatory logic inBacillus subtilisenabling the cell to directly monitor its need for detoxification. This cost-effective strategy is achieved via a two-component regulatory system (BceRS) working in a sensory complex with an ABC-transporter (BceAB), together acting as a flux-sensor where signaling is proportional to transport activity. How this is realized at the molecular level has remained unknown. Using experimentation and computation we here show that the histidine kinase is activated by piston-like displacements in the membrane, which are converted to helical rotations in the catalytic core via an intervening HAMP-like domain. Intriguingly, the transporter was not only required for kinase activation, but also to actively maintain the kinase in its inactive state in the absence of antibiotics. Such coupling of kinase activity to that of the transporter ensures the complete control required for transport flux-dependent signaling. Moreover, we show that the transporter likely conserves energy by signaling with sub-maximal sensitivity. These results provide the first mechanistic insights into transport flux-dependent signaling, a unique strategy for energy-efficient decision making.
引用
收藏
页码:157 / 174
页数:18
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