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Influence of external potassium on the rifampicin susceptibility of Mycobacterium

V Srinivasan(1,2) M Mauri(1,2) N L Quang(3) D D A Thu(3) B T B Hanh(3) T T B Tram(3) N T T Thuong(3,4) R Allen(1,2)

1:Theoretical Microbial Ecology Group, Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University Jena, Jena, Germany; 2:Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, Jena, Germany; 3:Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; 4:Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, United Kingdom

Mycobacterium tuberculosis causes tuberculosis (TB) a major human pulmonary infection with around 10 million cases per year. TB treatment requires minimum 6 months of antibiotic treatment, as persistent sub-populations of pathogen are tolerant to antibiotics. In this study we investigate the influence of external potassium concentration on rifampicin susceptibility of Mycobacterium species, since rifampicin is a core component of the TB treatment regimen. External potassium in the growth medium increased the rifampicin resistance of the lab model organism Mycobacterium smegmatis, increasing the minimum inhibitory concentration by more than 2-fold. Growth curve analysis revealed that potassium affects the lag time but not the growth rate at different rifampicin concentrations. Furthermore, we investigated the influence of potassium on the rifampicin susceptibility of a small set of clinical M. tuberculosis isolates. Taken together, our study reveals the influence of external factors such as potassium on the efficacy of rifampicin treatment and Mycobacterium growth dynamics. Understanding the molecular mechanism of this interaction will help in exploring possible potentiators of rifampicin action to improve TB treatment.

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