Multiple antibiotic resistance in South African strains of Streptococcus pneumoniae: mechanism of resistance to beta-lactam antibiotics. Rev Infect Dis

Multiply antibiotic-resistant strains of Streptococcus pneumoniae appeared in South Africa in 1977. In these organisms resistance to chloramphenicol is caused by an induci-ble, drug-inactivating enzyme; however, the basis for resistance to other antibiotics is unknown. Pneumococci with increased resistance to {3-lactam antibiotics do not pro-duce {3-lactamases, a finding indicating the presence of intrinsic resistance to these drugs. One approach to the understanding of the mechanism of this resistance was to study the pattern of penicillin-binding proteins (PBPs) in the South African pneumococci. With the use of highly radioactive penicillin to label PBPs in vivo, it was found that the South African pneumococci have a PBP pattern that differs from that of the sensitive laboratory strain R6 in several respects. Differences include (1) a lack of PBPs la and lb; (2) the presence of a new, faster moving protein (lower molecular weight), named PBP Ie; (3) an apparent decrease in the affinity of PBP 2a for pH]penicillin; and (4) a lack of PBP 2b. Taking advantage of the fact that penicillin resistance is a property acquired in a stepwise process, a series of isogenic and progressively more resistant transformants was constructed. DNA from the resistant South African strain 8249 of S. pneumonia