ABSTRACT
For several clinically important combinations of pathogen and antibiotic, the primary cause of antibiotic resistance is mutation or gene acquisition resulting in target alteration. These altered antibiotic targets are often the products of normal housekeeping genes on the chromosome, but they can also arise from horizontal genetic transfer and recombination, resulting in the creation of novel genetic mosaics. Our choice of examples covers the main antibiotic targets and is focussed on clinically important pathogens such as Streptococcus pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus, and Escherichia coli. In each case we relate the antibiotic target to clinically relevant antibiotics and pathogens. The extent of the resistance problem and the genetic basis of the alterations to the antibiotic target are discussed with reference to information from both in vitro selections and clinical isolates.
