Penicillin tolerance in multiply drug-resistant natural isolates of Streptococcus pneumoniae.

Five of six multiply drug-resistant clinical isolates of Streptococcus pneumoniae from South Africa demonstrated penicillin tolerance. In contrast to the common wild-type strains of pneumococci, treatment of the tolerant strains with penicillin above the minimum inhibitory concentration did not induce cell wall degradation, lysis, or leakage of intracellular components, and the rate of loss of viability was reduced compared with that of nontolerant strains. While these South African strains contained lower specific activity of autolytic enzyme than did nontolerant strains, the residual autolytic activity (15%-26% of the nontolerant wild type) was much more than that found in lysis-defective laboratory mutants of pneumococci (less than or equal to 1%); the rate of penicillin-induced lysis did not correlate with the specific activity of residual autolysin. Also, in contrast to the complete lysis resistance of lysis-defective mutants to all lytic agents, the tolerant South African strains were resistant primarily to lysis by beta-lactam antibiotics but could still be lysed by other cell wall inhibitors (e.g., cycloserine) and detergents. The penicillin resistance and penicillin tolerance traits could be separated by genetic transformation. We suggest that the drug-specific tolerance of the South African pneumococcal strains is related to some alteration in the control of autolysin activity.