Inhibition of peptidoglycan, ribonucleic acid, and protein synthesis in tolerant strains of Streptococcus mutans.
Exposure of exponentially growing cultures of Streptococcus mutans strains FA-1 and GS-5 to various concentrations of benzylpenicillin (Pen G) resulted in inhibition of turbidity increases at low concentrations (0.02 to 0.04 mug/ml). However, in contrast to some other streptococcal species, growth inhibition was not accompanied by cellular lysis or by a rapid loss of viability. In both strains, synthesis of insoluble cell wall peptidoglycan was very sensitive to Pen G inhibition and responded in a dose-dependent manner to concentrations of about 0.2 and 0.5 mug/ml for strains GS-5 and FA-1, respectively. Higher Pen G concentrations failed to inhibit further either growth or insoluble peptidoglycan assembly. Somewhat surprisingly, Pen G also inhibited both ribonucleic acid (RNA) and protein syntheses, each in a dose-dependent manner. Compared with inhibition of peptidoglycan synthesis, inhibition of RNA and protein syntheses by Pen G was less rapid and less extensive. Maximum amounts of radiolabeled Pen G were specifically bound to intact cells upon exposure to about 0.2 and 0.5 mug/ml of Pen G for strains GS-5 and FA-1, respectively, concentrations consistent with those that resulted in maximum or near-maximum inhibitions of the synthesis of cellular peptidoglycan, RNA, and protein. Five polypeptide bands that had a very high affinity for [(14)C]Pen G were detected in a crude cell envelope preparation of strain FA-1. After exposure of cultures of strain FA-1 to the effects of saturating concentrations of the drug for up to 3 h, addition of penicillinase was followed by recovery of growth after a lag. The length of the lag before regrowth depended on both Pen G concentration and time of exposure. On the basis of these and other observations, it is proposed that the secondary inhibitions of cellular RNA or protein synthesis, or both, are involved in the tolerance of these organisms to lysis and killing by Pen G and other inhibitors of insoluble peptidoglycan assembly.
D001329:Autolysis; D001426:Bacterial Proteins / Q000096:biosynthesis*; D004269:DNA, Bacterial / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000378:metabolism / Q000494:pharmacology*; D010403:Penicillin Resistance; D010457:Peptidoglycan / Q000096:biosynthesis*; D011485:Protein Binding; D012329:RNA, Bacterial / Q000096:biosynthesis*; D013295:Streptococcus mutans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D014640:Vancomycin / Q000494:pharmacology
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D010457:Peptidoglycan; D012329:RNA, Bacterial; D014640:Vancomycin; D010400:Penicillin G