Adaptor protein ClpS is an essential regulator of prokaryotic ATP-dependent protease ClpAP, which delivers certain protein substrates with specific amino acid sequences to ClpAP for degradation. However, ClpS also functions as the inhibitor of the ClpAP-mediated protein degradation for other proteins. Here, we constructed the clpS-overexpression Mycobacterium smegmatis strain, and showed for the first time that overexpression of ClpS increased the resistance of M. smegmatis to rifampicin that is one of most widely used antibiotic drugs in treatment of tuberculosis. Using quantitative proteomic technology, we systematically analyzed effects of ClpS overexpression on changes in M. smegmatis proteome, and proposed that the increased rifampicin resistance was caused by ClpS-regulated drug sedimentation and drug metabolism. Our results indicate that the changes in degradation related proteins enhanced drug resistance and quantitative proteomic analysis is an important tool for understanding molecular mechanisms responsible for bacteria drug resistance.
ATP-Dependent Proteases ; metabolism ; Drug Resistance, Bacterial ; Endopeptidase Clp ; metabolism ; Mycobacterium smegmatis ; drug effects ; metabolism ; Proteolysis ; Proteomics ; Rifampin ; pharmacology

Tuberculosis(TB) caused by the Mycobacterium tuberculosis(Mtb) is a worldwide public health threat.Microbiota in body affects human health and is involved in human diseases, and its clinical importance is begi-nning to be understood.In this review, studies on the relationship between the establishment of Mtb infection and microbiota as well as the development and antibiotic treatment of Mtb infection were discussed.Studies have shown that: (1) microbiota influences the establishment of Mtb infection; (2) co-infection of Helicobacter pylori alters susceptibility to Mtb infection and progression of active TB; (3) microbiota influences the progression of TB by regulating the nutritio-nal, metabolic and immune status of the host; (4) susceptibility to reinfection increases in TB patients treated with antibiotics, possibly due to T-cell epitope depletion of common intestinal non-Mtb Mycobacterium, the effects of antibio-tics are long-term in patients; (5) the occurrence of childhood TB is age-related and many factors such as co-infection and vaccine inoculation increase risk.An in-depth study of the relationship between the microbiota and TB will provide a new perspective on the prevention of TB.

Amino Acid Sequence ; Genes, Bacterial ; Hydrogen Peroxide ; pharmacology ; Molecular Sequence Data ; Mutation ; genetics ; Mycobacterium ; drug effects ; genetics ; growth & development ; Peptides ; chemistry ; metabolism ; Stress, Physiological ; drug effects

Anti-Bacterial Agents ; chemistry ; pharmacology ; Drug Resistance, Bacterial ; drug effects ; Humans ; Mycobacterium tuberculosis ; chemistry ; drug effects ; Tuberculosis, Multidrug-Resistant ; drug therapy ; microbiology