Abstract
BackgroundMortality due to tuberculosis (TB) has increased due to the development of drug resistance, the mechanisms of which have not been fully elucidated. Our research group identified a low expression of lipF gene in Mycobacterium tuberculosis clinical isolates with drug resistance. The aim of this work was to evaluate the effect of lipase F (LipF) expression on mycobacterial drug resistance.ResultsThe effects of expressing lipF from Mycobacterium tuberculosis in Mycobacterium smegmatis on resistance to antituberculosis drugs were determined with resazurin microtiter assay plate and growth kinetics. Functionality of ectopic LipF was confirmed. LipF expression reduced the rifampicin (RIF) and streptomycin (STR) minimum inhibitory concentration (MIC) from 3.12 μg/mL to 1.6 μg/mL and 0.25 μg/mL to 0.06 μg/mL respectively, moreover a reduced M. smegmatis growth in presence of RIF and STR compared with that of a control strain without LipF expression (p < 0.05 and p < 0.01) was shown.ConclusionsLipF expression was associated with increased RIF and STR sensitivity in mycobacteria. Reduced LipF expression may contribute to the development of RIF and STR resistance in Mycobacterium species. Our findings provide information pertinent to understanding mycobacterial drug resistance mechanisms.
Highlights
Mortality due to tuberculosis (TB) has increased due to the development of drug resistance, the mechanisms of which have not been fully elucidated
Nucleotide sequence comparison between pansensitive and multidrug resistant (MDR) strains Nucleotide sequence analysis were performed on the promoter and coding sequences of lipF to determine whether differential expression between the pansensitive
lipase F (LipF) expression in Mycobacterium smegmatis To elucidate the role of Lipase F in drug resistance, we evaluated the effects of overexpressing it in a M. tuberculosis surrogate, M. smegmatis
Summary
Mortality due to tuberculosis (TB) has increased due to the development of drug resistance, the mechanisms of which have not been fully elucidated. Our research group identified a low expression of lipF gene in Mycobacterium tuberculosis clinical isolates with drug resistance. The aim of this work was to evaluate the effect of lipase F (LipF) expression on mycobacterial drug resistance. A clinical MDR M. tuberculosis isolate was reported to have differential gene expression compared with that in the pansensitive H37Rv strain. In a recent study of 24 clinical isolates of M. tuberculosis with varying drug resistance profiles and genetic backgrounds, lipF expression was found to be reduced in ~ 90% of these resistance strains compared with that in the pansensitive reference strain H37Rv [19]. The aim of the present work was to evaluate the effect of lipF expression on drug resistance in a M. tuberculosis surrogate
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