Abstract
Transport-related genes significantly affect bacterial antibiotic resistance. However, the effects of these genes and their regulation of bacterial drug resistance in several mycobacterial species, including the fast-growing Mycobacterium smegmatis, the pathogen M. tuberculosis and M. avium have not been clearly characterized. We identified Ms4022 (MSMEG_4022) as a novel TetR family regulator that activates the expression of seven transport-related genes and affects drug resistance in M. smegmatis. Overexpression of Ms4022 inhibited M. smegmatis growth and enhanced mycobacterial resistance to the anti-tuberculosis drug rifampicin (RIF). By contrast, the Ms4022-deleted mycobacterial strain has shown sensitive to RIF. Ms4022 recognized three 19 bp non-palindromic motifs containing a 9 bp conserved region at their 5′ end and it directly regulated seven transport-related genes, which affects mycobacterial resistance to RIF. Overexpression of three of seven transport-related genes (Ms1448, Ms1613, and Ms5278) inhibited the growth of M. smegmatis. This study improves our understanding of the function of mycobacterial transport-related genes and their regulation of bacterial drug resistance.
Highlights
Transport-related genes are encoded by the genome of M. smegmatis (GenBank accession number CP000480)
These results suggest that the TetR family regulator, Ms4022, contributes to the RIF resistance of M. smegmatis
We proved that the overexpression of Ms4022 caused RIF resistance in M. smgmatis through elevated levels of transport-related genes
Summary
Transport-related genes are encoded by the genome of M. smegmatis (GenBank accession number CP000480). The physiological roles of these regulators and transport-related genes and their relationships with bacterial drug resistance remain unknown. We characterize a new TetR family transcriptional factor, Ms4022, as a positive regulator in M. smegmatis. Ms4022 activates the expression of seven transport-related genes and affects the RIF resistance and growth of M. smegmatis. This study enhances our understanding of transport-related gene regulation and drug resistance in mycobacteria
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