Effects of mecillinam and cefoxitin on growth, macromolecular synthesis, and penicillin-binding proteins in a variety of streptococci.

Although some strains of streptococci seem to be virtually inert to mecillinam, the growth of other strains, notably certain viridans streptococci (Streptococcus mutans and Streptococcus sanguis) was inhibited by relatively low concentrations of the drug. Inhibition of the synthesis of peptidoglycan, RNA, protein, and DNA in two tolerant strains, S. mutans FA-1 and GS-5, was studied over a wide range of concentrations of mecillinam, benzylpenicillin, and cefoxitin. The responses of both strains to all three beta-lactams were very similar; that is, synthesis of insoluble peptidoglycan was most susceptible. Inhibition of peptidoglycan synthesis was followed rapidly and sequentially by substantial but less severe inhibitions of RNA and protein synthesis. Significant inhibition of DNA synthesis was not observed. Binding studies with [14C]benzylpenicillin alone or after preexposure of membrane preparations to benzylpenicillin, mecillinam, or cefoxitin suggest that reasonably selective binding of a beta-lactam antibiotic to one or two of the major penicillin-binding proteins (PBP 1 or PBP 4) of S. mutans GS-5 and FA-1 may be the initial step in the series of events that results in the inhibition of growth and in the inhibition of insoluble peptidoglycan assembly and of RNA and protein synthesis.