Sub-minimum inhibitory concentration of rifampin: A potential risk factor for resuscitation of Mycobacterium tuberculosis

Abstract

Background: Mycobacterium tuberculosis possesses five resuscitation-promoting factors, Rpf A to E, which are required for the resuscitation of dormancy in mycobacteria. This study explores the transcriptional profile of all five rpfs of M. tuberculosis, in response to sub-MIC concentration of rifampin, in multidrug and mono-rifampin resistant clinical isolates. Methods: Thirteen multidrug and two rifampin mono resistant clinical isolates were analyzed. Drug susceptibility testing and determination of MIC were performed. The relative expression of rpfs was measured, by real-time quantitative PCR. Results: A significant upregulation of relative expression (p < 0.05) was observed, as follows: 7/15(46.66%); 5/15(33.33%); 9/15(60%); 10/15(66.66%) and 9/15(60%) in rpfA, rpfB, rpfC, rpfD and rpfE, respectively. Conclusion: Our results showed that the rpfs could be overexpressed in some extent in the presence of sub-MIC concentration of rifampin in multidrug and mono drug resistant M. tuberculosis. These results highlight the potential risk of sub-MIC rifampin concentrations, as a risk factor for tuberculosis reactivation.