Small changes in enzyme function can lead to surprisingly large fitness effects during adaptive evolution of antibiotic resistance.

ABSTRACT: In principle, evolutionary outcomes could be largely predicted if all of the relevant physicochemical variants of a particular protein function under selection were known and integrated into an appropriate physiological model. We have tested this principle by generating a family of variants of the tetracycline resistance protein TetX2 and identified the physicochemical properties most correlated with organismal fitness. Surprisingly, small changes in the K(m(MCN)), less than twofold, were sufficient to produce highly successful adaptive mutants over clinically relevant drug concentrations. We then built a quantitative model directly relating the in vitro physicochemical properties of the mutant enzymes to the growth rates of bacteria carrying a single chromosomal copy of the tet(X2) varian

SUBMITTER: Walkiewicz K 

PROVIDER: S-EPMC3535585 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature