Because of mutations, the concept that all cells arising from a single cell are identical is not strictly true, since every large population contains mutants. Even the cells in a single colony that contains about 1 million cells are not completely identical because of random mutations. These mutations provide a mechanism by which organisms, with their altered characteristics, can respond to a changing environment. This is the process of natural selection. The environment, however, does not cause the mutation but rather selects those cells that can grow under its conditions. Thus, a spontaneous mutation to antimicrobial resistance, though rare, will result in the mutants becoming the dominant organisms in a hospital environment where the antimicrobial medication is present, because only the resistant cells can survive. The antimicrobial kills the sensitive cells and thereby allows the resistant cells to take over the population.
Since genes mutate independently of one another, the chance that two given mutations will occur within the same cell is very low. Indeed, the actual occurrence is the product of the individual rates of mutation of the two genes (calculated by taking the sum of the exponents). For example, if the mutation rate to streptomycin resistance is 10:6 per cell division and the mutation rate to penicillin resistance is 10:8 per cell division, the probability that both mutations will occur within the same cell is 10:6 x 10:8, or 10:14. For this reason, two or more drugs may be administered simultaneously in the treatment of some diseases such as tuberculosis and AIDS. This is called combination therapy. Any mutant cell or virus resistant to one antimicrobial medication is likely to be sensitive to the other and therefore will be killed by the combination of the two antimicrobials. ■ combination therapy, p. 750
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