Van Breda, Shane VontelinBuys, AntoinetteApostolides, ZenoNardell, Edward AnthonyStoltz, Anton Carel2015-07-012015-07-012015-07Van Breda, SV, Buys, A, Apostolides, Z, Nardell, EA & Stoltz, AC 2015, 'The antimicrobial effect of colistin methanesulfonate on Mycobacterium tuberculosis in vitro', Tuberculosis, vol. 95, no. 4, pp. 440-446.1472-9792 (print)1873-281X (online)10.1016/j.tube.2015.05.005http://hdl.handle.net/2263/45833Polymyxins have previously been described to have activity against M. tuberculosis (MTB), but further research was abandoned due to systemic toxicity concerns to achieve the required MIC. Colistin methanesulfonate (CMS), a polymyxin, is well tolerated when inhaled directly into the lungs, resulting in high local concentrations. We report here for the first time, MIC and MBC data for CMS determined by the microtiter Alamar Blue assay (MABA). We also determined how the MIC would be affected by the presence of pulmonary surfactant (PS) and if any synergy with isoniazid (INH) and rifampicin (RIF) exists. The effect of CMS on the ultrastructure of MTB was also determined. The MIC for CMS was 16 mg/L, while the MBC was 256 mg/L. MIC for CMS in PS was antagonised by eight fold. For synergy, indifference was determined while time-kill assays revealed a greater killing effect when CMS was used together with INH. Ultrastructure analysis suggests that the disruption of the outer polysaccharide layer of MTB by CMS may lead to enhanced uptake of INH. Our findings may provide insight for further investigations of CMS against MTB.en© 2015 Elsevier Ltd. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Tuberculosis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Tuberculosis, vol. 95, no. 4, pp. 440-446, 2015. doi : 10.1016/j.tube.2015.05.005Colistin methanesulfonateColistin sulfatePolymyxinSelfpromoted uptakeTuberculosis (TB)Mycobacterium tuberculosis (MTB)Postprint Article