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ClpS是原核生物蛋白质降解复合物ClpAPS的重要组成成分,它可以识别某些特定的氨基酸序列并将其呈递给ClpAP以促进其降解。同时,ClpS也抑制了其他蛋白质底物的降解。本研究通过在耻垢分枝杆菌中过度表达ClpS,发现所构建的重组菌株提高了利福平的抗药性。应用定量蛋白质组学技术,我们系统地分析了过度表达ClpS对于细菌蛋白质组的影响,并推测出细菌抗利福平的分子机制:ClpS促进稳态的调整、促进药物沉降以及加速药物代谢。本研究首次通过改变细菌降解复合物的相关蛋白的表达增加细菌的抗药性,并证明蛋白质组学技术是细菌的抗药性研究以及耐药株筛选的重要工具。
ClpS is an important component of prokaryotic protein degradation complex ClpAPS, it can identify certain specific amino acid sequence and presented to ClpAP to promote its degradation. At the same time, ClpS also inhibits the degradation of other protein substrates. In this study, ClpS was overexpressed in Mycobacterium smegmatis, and the constructed recombinant strain was found to increase the resistance of rifampicin. Using quantitative proteomics, we systematically analyzed the effect of overexpression ClpS on bacterial proteomes and speculated the molecular mechanism of bacterial anti-rifampin: ClpS promotes homeostasis, promotes drug deposition, and accelerates drug metabolism. This study, for the first time, enhanced bacterial resistance by altering the expression of related proteins in the bacterial degrading complex and demonstrated that proteomics is an important tool for bacterial resistance and screening of resistant strains.