How do bacteria become resistant to antibiotics? They evolve! They evolve quickly too, in a study conducted by Watson et al, mutant strains of Escherichia coli (E. coli) with resistance to the antibiotic trimethoprim (TMP) were obtained after only three generations. How is this possible? Well, taking into account the popular theory of directed evolution, results from this study show that not only can E. coli mutate to overcome the effects of TMP, but the bacterium has the ability to simultaneously increase enzymatic activity, which also reduces the effect of TMP.
Directed evolution was used in this study as a protocol to simulate natural evolutionary processes. Dihydrofolate reductase (DHFR), the target of the antifolate TMP, developed reduced binding affinity for the drug as a result of several mutations. Thus DHFR, with its huge evolutionary potential, does not make it a suitable drug target. It was concluded therefore that locating enzymes which are “at or near their evolutionary limit” (Watson et al, 2007) will be a viable direction for the future design of effective antibacterial drugs. So the bacterial mutations of today, whilst dodging the effects of current antibiotics, will eventually be tackled by drugs specifically aimed at the mega-evolved enzymes of tomorrow!
References:
Watson M, Liu J and Ollis, D, 2007, Directed evolution of trimethoprim resistance in Escherichia coli, FEBS Journal, vol 274, pp 2661-2671.
