Effect of Antibiotics on Sporulation Caused by the Stringent Response in Bacillus subtilis

Abstract

Summary: We have examined in Bacillus subtilis how antibiotics that inhibit protein or RNA synthesis affect the stringent response (i.e. accumulation of (p)ppGpp) and the resulting decrease of GTP and sporulation. All antibiotics used inhibited sporulation completely at concentrations at which they inhibited growth only partially and in most cases only slightly. At these concentrations, some antibiotics (chloramphenicol, fusidic acid, lincomycin. tetracycline) abolished the stringent control, others lowered it. Sporulation inhibited by chloramphenicol or fusidic acid could be almost completely restored by addition of 0.2-0.5 mM-decoyinine, an inhibitor of GMP synthetase. The inhibition of sporulation by tetracycline and streptomycin, or by the RNA polymerase inhibitors rifampin and lipiarmycin, was partially counteracted by decoyinine, whereas the inhibition by lincomycin or by compounds that did not interfere with the stringent response could not be overcome by decoyinine addition. In mutants resistant to erythromycin, or lincomycin or thiostrepton, sporulation was no longer inhibited by that particular antibiotic but was still sensitive to the other two. The results show that some antibiotics inhibited sporulation because they prevented the decrease of GTP needed to initiate sporulation caused by the stringent response. Other antibiotics inhibited sporulation by interfering with specific (ribosomal) functions either needed to maintain a certain metabolic state or specifically required for the synthesis of sporulation-specific proteins.