A Practical Guide to Measuring Mutation Rates in Antibiotic Resistance

Bacteria become resistant to antibacterial agents by three main mechanisms: acquisition of complete resistance genes or gene complexes via plasmids and other transposable elements (12, 16, 21, 26, 30), recombination of DNA from other bacteria into the genome by transformation (6), and spontaneous mutational events in the chromosome and accessory DNA (14). Horizontal gene transfer in bacteria has been reviewed by Thomas and Nielsen (31). This minireview will concentrate on the study of chromosomal mutations that confer resistance. Mutational events are assumed to be stochastic, so that the rate of beneficial mutation does not occur at a higher frequency than those that are neutral or disadvantageous and that mutations are not directed. For bacterial cells, there is a finite probability that a mutation conferring the resistant phenotype will occur, and unless a revertant mutation occurs, all of the progeny of such a cell will be resistant also. An important review by Rosche and Foster which critically analyzes mutation rate determination methods lays the foundation of this minireview (29). The terms and abbreviations used here are defined in Table ​Table11.