Are phylogenetic position, virulence, drug susceptibility and in vivo response to treatment in mycobacteria interrelated?

Phylogenetic analyses on the basis of multiple house-keeping genes and whole genome sequences have offered new insights in the phylogeny of the genus Mycobacterium. This genus yields obligate pathogens, the M. tuberculosis complex and M. leprae, as well as opportunistic pathogens (e.g. M. avium, M. intracellulare, M. kansasii, M. marinum, M. malmoense) and saprophytes (e.g. M. phlei, M. sphagni, M. gordonae). The most virulent mycobacteria, the M. tuberculosis complex, M. leprae and the M. kansasii-M. szulgai-M. marinum-M. ulcerans group are phylogenetically related and infections by these organisms are better treatable than those caused by less virulent and phylogenetically more distantly related Mycobacterium species. The most virulent Mycobacterium species are also characterized by high levels of natural drug susceptibility. In this paper, we review studies of phylogeny, drug susceptibility, and clinical significance to support our hypothesis that drug susceptibility in mycobacteria is acquired and reflects the low level of competition in -and adaptation to- a closer-to-human (environmental) niche. In turn, mycobacteria that inhabit the most competitive environmental niches are the least adapted to humans, thus of low clinical significance, but most tolerant to antibiotics derived from microbes with which they share their habitat, lowering the chances of cure in case of infection.

Synergistic effect of rifampin, streptomycin, ethionamide, and ethambutol on Mycobacterium intracellulare

A method of quantitative estimation to determine the interaction of antituberculosis drugs is suggested. The design of experiments, performed on 7H11 agar plates, is adjusted to the following statistical treatment by combined use of probit analysis and isobologram methods. By plotting the values reflecting the inhibition of 75% of the bacterial population (ED75) with their confidence limits on the isobologram, it was found that the clearest results proving synergism between the drugs could be obtained. Six 2-drug combinations and 6 3-drug combinations were tested against strains of Mycobacterium intracellulare (serovar 8), and a synergistic effect was demonstrated in most of them. These were various combinations of rifampin, streptomycin, ethambutol, and ethionamide. The application of probit analysis to the data derived from testing single drugs can provide a quantitative estimation of the actual drug resistance of the M. intracellulare strains.