Further studies on colistin (polymyxin E)-induced cell leakage in mycobacteria: Mg++ efflux in Mycobacterium avium and its effects on drug-susceptibility.
Action of colistin (polymyxin E) was investigated on the opportunistic pathogenic species Mycobacterium avium ATCC 15769 (resistant strain, MIC greater than 100 micrograms/ml). Mycobacterium intracellulare ATCC 13950: a colistin-susceptible strain (MIC 25 micrograms/ml), was used as a parallel control for Mg++ efflux experiments. After the addition of 100 micrograms/ml of colistin to bacteria suspended in a buffer, both loss of viability and Mg++ efflux were followed for one week. Although there was an initial Mg++ efflux in 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 attained 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 cytoplasmic Mg++ efflux solely, but some additional effect was implicated. The drug-susceptibility of extracellularly-growing and intracellularly-growing (in the J-774 macrophage cell line) M. avium to the antibiotics tested could not be potentiated when they were used in combination with 5 micrograms/ml of colistin (maximal obtainable serum level in man) or the polymyxin B nonapeptide (PMBN), nor in the case of bacteria pretreated with these molecules.
Rastogi
N
N
Service de la Tuberculose et des Mycobactéries, Institut Pasteur, Paris, France.
Potar
M C
MC
Henrotte
J G
JG
Franck
G
G
David
H L
HL
D000658:Amoxicillin / Q000494:pharmacology; D002228:Carbenicillin / Q000494:pharmacology; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology; D003091:Colistin / Q000494:pharmacology*; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism*; D009162:Mycobacterium avium / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
D002969:Clavulanic Acids; D019818:Clavulanic Acid; D000658:Amoxicillin; D002228:Carbenicillin; D008274:Magnesium; D003091:Colistin