Talk-back regulation: a regulatory response to the inhibitions of cell surface growth.

The net accumulation of RNA and protein was studied in exponentially growing cultures of Streptococcus rattus FA-1 (formerly S. mutans FA-1) during periods of antibiotic induced inhibition of cell surface growth. Disruption of either the cytoplasmic, membrane, or final assembly steps of peptidoglycan (PG) synthesis following exposure of cultures to D-cycloserine plus beta-chloro-D-alanine (CS-CA), vancomycin (Vanco) or benzylpenicillin (Pen G) respectively, was accompanied by a rapid inhibition of RNA accumulation followed by an inhibition of protein accumulation. At physiologically comparable concentrations, CS-CA and Vanco inhibited RNA more efficiently than Pen G. CS-CA inhibited RNA and PG to the same degree while RNA accumulation was clearly more sensitive to Vanco than was PG. Simultaneous treatment with chloramphenicol (CAP), relaxed the cell wall antibiotic induced inhibition of RNA to a degree and with kinetics similar to those observed during CAP relaxation of the stringent response in amino acid deprived cultures. The degree of survival following exposure to the PG inhibitors varied directly with the efficiency of the antibiotics to inhibit RNA accumulation. CAP and tetracycline acted synergistically with CS-CA and to a lesser degree with Vanco while marginally antagonizing the killing effects of Pen G. On the basis of these and other observations it is proposed that the assembly status of the cell wall can be communicated, i.e. 'talk back', to the cytoplasmic processes of macromolecular synthesis via a specific regulatory type circuit. The efficiency of induction of the talk-back response appears to be directly related to survival.