Antioxidant functions required for insusceptibility of Saccharomyces cerevisiae to tetracycline antibiotics

Abstract

Cu,Zn superoxide dismutase (Sod1) is required for insusceptibility of Saccharomyces cerevisiae to oxytetracycline (OTC). Here we report that Sod1 is also required for insusceptibility to doxycycline (DOX). Furthermore, among a range of antioxidant and redox balance mutants, mac1 and ctr1 deletion strains exhibited marked sensitization to OTC and DOX. Certain mutants exhibited a slight sensitivity to methacycline and minocycline. Addition of copper suppressed antibiotic sensitivity. Thus, intracellular copper as well as superoxide dismutase can be critical for eukaryotic tolerance of several tetracycline antibiotics.

FIG. 1

Susceptibilities of antioxidant-deficient and redox balance-deficient S. cerevisiae mutants to OTC. Dilutions of decreasing cell concentration were spotted from left to right on each plate. S. cerevisiae sod2Δ, ctt1Δ, gsh1Δ, ogg1Δ, gpx1/2/3Δ, mxr1Δ, yap1Δ, and fre1Δ mutants were unaffected by OTC (not shown). Typical results from one of three independent experiments are shown.

FIG. 2

Structures of the tetracyclines.

FIG. 3

Susceptibilities of antioxidant-deficient and redox balance-deficient S. cerevisiae mutants to a range of tetracyclines. Dilutions of decreasing cell concentration were spotted from left to right on each plate. Results are shown for doxycycline (DC) (A) and for methacycline (MTC) and minocycline (MNC) (B). Note that spots were smaller with MTC due to the surface tension imparted by the antibiotic. The mutants were not affected by TET or CTC (not shown). Typical results from one of three independent experiments are shown.