Zbl. Bakt. Hyg. A 268, 251-258 (1988) Further Studies on Colistin (Polymyxin Ej-Induced Cell Leakage in Mycobacteria: Mg ++ Efflux in Mycobacterium avium and its Effects on Drug-Susceptibility NALIN RASTOGI! ", MARIE-CHRISTINE POTAR], JEAN-GEORGES HENROTTE 2 , GISELE FRANCK 2 , and HUGO L. DAVID] ] Service de la Tuberculoseet des Mycobacteries, Institut Pasteur, 75015 Paris, France 2 Centre National de la RechercheScientifique, Faculte de Pharmacie, 75006 Paris, France With 5 Figures· Received June 18, 1987· Accepted September21, 1987 Abstract Action of colistin (polymyxin E) was investigated on the opportunistic pathogenic species Mycobacaterium avium ATCC 15769 (resistant strain, MIC > 100 ug/ml), Mycobacterium intracellulare ATCC 13950: a colistin-susceptible strain (MIC 25 ug/ml), was used as a parallel control for Mg++ efflux experiments. After the addition of 100 ug/mlof colistinto bacteria suspended in a buffer, both loss of viabilityand Mg++ efflux were followed for one week. Although there was an initial Mg++ effluxin both strains, it soon attained a plateau in case of the resistant strain without any loss of viability until 48 h, whereas in case of the susceptible strain, Mg++ efflux was about 3 times higher than former, a plateau was at- tained only 24 h after the drug addition, and the loss of viability started only 6 h after the drug addition. Consequently,the loss of viability of M. avium with later incubation times (6 days) was not due to the action of colistin on the cytoplasmicMg'" efflux solely, but some additional effect was implicated. The drug-susceptibility of extracellularly-growing and intracellularly-growing (in the J-774 macrophagecellline)M. aviumto the antibiotics tested could not be potentiated when they were used in combination with 5 ug/rnl of colistin (maximal obtainable serum level in man) or the polymyxin B nonapeptide (PMBN), nor in the case of bacteria pretreated with these molecules. Zusammenfassung Die Wirkung von Colistin (Polymyxin E) wurde an dem opportunistischen Erreger My- cobacterium avium ATCC 15769 (resistenterStamm, MHK > 100 ug/ml) untersucht. Der Colistin-empfindliche Stamm ATCC 13950 von Mycobacterium intracellulare (MHK 25 ug/rnl) diente als parallele Kontrolle bei Versuchen zum Mg++Efflux. Nach Zugabe von 100 !-tg/ml Colistin zu in Puffer suspendiertenBakterienwurden eine Woche lang der Verlust der Vermehrungsfahigkeit und Mg++-Efflux verfolgt, Obwohl es bei beiden Stammen zu einem anfanglicben Mg++-Efflux kam, erreichte dieser bei dem resistenten Stamm schnell • Corresponding author.