Alterations in Penicillin-Binding Proteins of Clinical and Laboratory Isolates of Pathogenic Streptococcus pneumoniae with Low Levels of Penicillin Resistance

Abstract

Several recent surveys of clinical isolates have indicated that substantial fractions of naturally occurring populations of Streptococcus pneumoniae have undergone a distinct upward move in the required minimal inhibitory concentration (MIC) of benzylpenicillin (from a range of 0.006–0.008 to 0.03–0.05 µg/ml). Evidence is presented that in clinical pneumococcal isolates, penicillin-binding proteins (PBPs) groups 1 and 2 have a decreased affinity for radioactive benzylpenicillin as compared with penicillin-sensitive isolates from the same locale. Exposure of a penicillin-sensitive type 2 strain (MIC, 0.006 µg/ml) to sequentially increasing concentrations of penicillin allowed the isolation of spontaneous resistant mutants with stepwise increases in the MIC of penicillin required (0.01–0.02, 0.025–0.05, and 0.1 µg/ml), and in these laboratory isolates too, PBP groups 1 and 2 showed decreased affinity for labeled benzylpenicillin. DNA from the low-level resistant clinical or laboratory isolates could be used to transform the appropriate levels of penicillin resistance into penicillin-sensitive laboratory isolates. These findings suggest that significant fractions of natural pneumococcal populations may have acquired one or two of the low-level penicillin resistance genes.