Frequency, spectrum, and nonzero fitness costs of resistance to myxopyronin in Staphylococcus aureus.

ABSTRACT: The antibiotic myxopyronin (Myx) functions by inhibiting bacterial RNA polymerase (RNAP). The binding site on RNAP for Myx-the RNAP "switch region SW1/SW2 subregion"-is different from the binding site on RNAP for the RNAP inhibitor currently used in broad-spectrum antibacterial therapy, rifampin (Rif). Here, we report the frequency, spectrum, and fitness costs of Myx resistance in Staphylococcus aureus. The resistance rate for Myx is 4 × 10(-8) to 7 × 10(-8) per generation, which is equal within error to the resistance rate for Rif (3 × 10(-8) to 10 × 10(-8) per generation). Substitutions conferring Myx resistance were obtained in the RNAP β subunit [six substitutions: V1080(1275)I, V1080(1275)L, E1084(1279)K, D1101(1296)E, S1127(1322)L, and S1127(1322)P] and the RNAP β' subunit [five subs

SUBMITTER: Srivastava A 

PROVIDER: S-EPMC3497154 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature