GENETICS AND MOLECULAR-BIOLOGY OF BETA-LACTAM-RESISTANT PNEUMOCOCCI

Penicillin-resistant pneumococci have been reported with increasing fr equency in recent years, Isolates with high-level resistance are now f ound in many countries, and in some countries they constitute a substa ntial proportion of all isolates, A worrying development is the recent emergence of pneumococci with high-level resistance to third-generati on cephalosporins, Resistance to beta-lactam antibiotics in pneumococc i is due entirely to the development of altered forms of the high-mole cular-weight penicillin-binding proteins (PBPs) that have decreased af finity for the antibiotics, High-level resistance to third-generation cephalosporins has occurred by the development of altered forms of PBP 1a and 2x, whereas high-level penicillin resistance additionally requi res alterations of PBP2b, Altered PBPs are encoded by mosaic genes tha t have emerged by recombinational events between the pbp genes of pneu mococci and their homologs in closely related streptococcal species, H orizontal gene transfer, presumably mediated by genetic transformation , has also resulted in the dissemination of altered pbp genes, and pos sibly capsular biosynthetic genes, between different pneumococcal line ages to produce new resistant clones.