James O. Kilburn

Inhibition by Ethambutol of Mycolic Acid Transfer into the Cell Wall of Mycobacterium smegmatis

Ethambutol simultaneously inhibited the transfer (presumably via mycolyl acetyl trehalose) of mycolic acids into the cell wall and stimulated the synthesis of trehalose dimycolates of Mycobacterium smegmatis. Structural similarities of the drug and mycolyl acetyl trehalose suggested that competitive inhibition was involved.

Effect of Ethambutol on the Viable Cell Count in Mycobacterium smegmatis

Soon after a strain of Mycobacterium smegmatis was exposed to ethambutol (EMB), the number of viable cells increased dramatically above the number in a drug-free control. This rapid rise did not occur when the culture was maintained at 4°C instead of 37°C, when an EMB-resistant mutant was used, when auxotrophs were exposed in medium lacking nutrients essential for growth, nor when the levo form of EMB was used. EMB caused no increase in deoxyribonucleic acid synthesis, nor in septum formation of dividing cells. Treated cells changed morphologically, resulting in a lower surface area-to-volume ratio. Whereas EMB did not eliminate cell clusters, the cluster size decreased markedly as detected by filtration and Coulter counter measurements. We concluded that EMB causes a reduced surface-to-volume ratio, leading to reduced cell cohesion and a consequent reduction in cluster size, reflected in an increase in colony-forming units. Images

Effects of Ethambutol on Phospholipid Metabolism in Mycobacterium smegmatis

Soon after Mycobacterium smegmatis was exposed to ethambutol, the synthesis of cardiolipin and phosphatidylinositol dimannoside declined. The synthesis of phosphatidylethanolamine continued, but the drug caused this phospholipid to leak out of the cells.

DIFFERENTIAL IDENTIFICATION OF MYCOBACTERIA VI. MYCOBACTERIUM TRIVIALE KUBICA SP. NOV.

ABSTRACT A new species of nonphot ochromogen mycobacteria is described. Most of the strains examined have been isolated from man; however, because of their lack of relationship to human disease, the name Mycobacterium triviale Kubica is proposed. The physical and biochemical characteristics, serologic activity, and thin layer chromatographic pattern of this new species serve to distinguish it from other nonphotochromo-genic mycobacteria in Runyons Group III.

Susceptibility of Mycobacteria to Rifampin

The Mycobacterium species M. tuberculosis, M. avium-intracellulare, M. kansasii, M. marinum, M. scrofulaceum, M. fortuitum, M. terrae, and M. gordonae were analyzed for their susceptibility to rifampin. M. tuberculosis, M. kansasii, and M. marinum were susceptible to the antibiotic, and resistant populations developed as a result of the interplay of mutation and selection. The mutation rates (susceptibility → resistance) were calculated to be 4.9 × 10−10 and 1.7 × 10−9 mutations per bacterium per generation in, respectively, M. kansasii and M. marinum. M. fortuitum was found to be naturally resistant to the antibiotic, whereas the nature of resistance in the other species was unclear and is discussed.