A mutant of group A streptococcus resistant to high levels of kanamycin exhibits characteristics of penicillin tolerance in vitro

In studies of penicillin tolerance in group A streptococci, we observed that a mutant of group A streptococcus isolated for high-level resistance to kanamycin exhibited several characteristics of penicillin tolerance: significant disparity between the penicillin MIC and MBC, delayed killing by penicillin concentrations of 16 times the MIC, and survival in areas of superinhibitory penicillin concentrations when strains were transferred from a penicillin-gradient plate to a penicillin-free replicate plate. In contrast, the parent strain of group A streptococcus and its mutant isolated for high-level resistance to streptomycin were nontolerant for penicillin. Moreover, a clinical isolate of group A streptococcus possessing high-level resistance to kanamycin was also found to be tolerant to penicillin. These findings suggest that genetic mechanisms responsible for high-level resistance to kanamycin may be related with the expression of penicillin tolerance of group A streptococci in vitro.