Effect of H2S and cysteine homeostasis disturbance on ciprofloxacin sensitivity of Escherichia coli in cystine-free and cystine-fed minimal medium
Endogenous H2S has been proposed to be a universal defense mechanism against different antibiotics. Here, we studied the
role of H2S transiently generated during ciprofloxacin (CF) treatment in M9 minimal medium with sulfate or produced by E.
coli when fed with cystine. The cysM and mstA mutants did not produce H2S, while gshA generated more H2S in response to ciprofloxacin in cystine-free media. All mutants showed a reduced ability to maintain cysteine homeostasis under these
conditions. We found no relationship between H2S generation, cysteine concentration and sensitivity to ciprofloxacin. Excess
cysteine, which occurred during E. coli growth in cystine-fed media, triggered continuous H2S production, accelerated glutathione synthesis and cysteine export. This was accompanied by a twofold increase in ciprofloxacin tolerance in all strains except gshA, whose sensitivity increased 5–8-fold at high CF doses, indicating the importance of GSH in restoring the intracellular redox situation during growth in cystine-fed media.
