HORIZONTAL GENETIC EXCHANGE, EVOLUTION, AND SPREAD OF ANTIBIOTIC-RESISTANCE IN BACTERIA

Some transformable bacteria have acquired target-mediated antibiotic r esistance by horizontal genetic exchange of fragments of chromosomal g enes. The resistant strains express variants of the antibiotic target that are metabolically active but exhibit a lowered affinity for the a ntibiotic. The alleles encoding these resistant proteins are mosaics c omprising DNA derived from the host and other bacteria, often members of a different species. Examples include penicillin-resistant penicill in-binding proteins (PBPs) in Streptococcus pneumoniae and the pathoge nic Neisseria species and sulfonamide-resistant dihydropterate synthas e in Neisseria meningitidis. Distinct mosaic alleles encoding antibiot ic resistance have arisen on multiple occasions, indicating the mobili ty of chromosomal genes in these species. Mosaic genes can arise at an y chromosomal locus, and S. pneumoniae organisms with high-level penic illin resistance have acquired mosaic PBP genes at three separate pbp loci. Furthermore, horizontal genetic exchange permits movement of all eles among bacterial lineages, increasing the opportunities for the sp read of antibiotic resistance.