Induction of resistance in Mycobacterium smegmatis.

In this work, we assayed the ability of newly prepared indolizine derivates (epimers) 6C and 6A to inhibit the growth of Mycobacterium smegmatis and used them for resistance induction. 6A inhibited the growth of M. smegmatis at a concentration of 100 μg/mL. No inhibitory effect was observed in the presence of 6C. By incubating the bacteria with 6C and 6A, colonies resistant to 6A were observed. Finally, 37 stable resistant strains were isolated. These resistant strains were able to grow on a 5-fold higher concentration of 6A (500 μg/mL) than the minimal inhibitory concentration of the wild type (100 μg/mL), with no growth inhibition. Resistant strains were then tested for cross-resistance to other antibiotics: ampicillin, tetracycline, ciprofloxacin, chloramphenicol, gentamicin, and streptomycin. Determinations of resistance patterns to 6 antibiotics revealed 36 strains that were resistant to at least one drug.