New mechanism of antibiotic resistance revealed
Low doses of antibiotics form drug resistance in mycobacteria without changing their DNA. Kanamycin, ofloxacin, and tetracycline significantly increase the activity of the main drug resistance regulator gene whiB7. At the same time, tetracycline provokes formation of cross-drug resistance to 9 or more antibiotics at once.Researchers from the Institute of Ecology of the Peoples' Friendship University of Russia, the Vavilov Institute of General Genetics, and the Institute of General Genetics. N.I. Vavilov Institute of Ecology of the Russian Federation and Bashkir State Agrarian University have studied the effect of small doses of antibiotics on the formation of drug resistance in mycobacteria. The results were published in the journal Biology.
It was found that kanamycin, ofloxacin and tetracycline at low doses significantly increased the activity of the main resistance-regulating gene whiB7. At the same time, tetracycline provokes the formation of cross-drug resistance to 9 or more antibiotics at once. In turn, ofloxacin suppresses the activity of the other 6 regulatory genes, which confirms the formation of drug resistance of mycobacteria to it through whiB7. As for streptomycin, it has no effect on the activity of the studied genes at all, while kanamycin does, and on several genes at once.
The mechanism of formation of resistance to anti-TB drugs differs from the classical one, in which mutations occur in bacterial DNA, the researchers note. This knowledge will help develop new methods to combat drug-resistant bacteria.
The scientists focused on the nonpathogenic M. smegmatis strain mc2 155, which has twice as many genes responsible for neutralizing various drugs. To avoid cross-resistance, the team chose the main antituberculosis antibacterials: kanamycin, streptomycin, ofloxacin, and tetracycline. To assess sensitivity, paper disks impregnated with drug solutions of different concentrations were used.