Lysis of nongrowing Escherichia coli by combinations of beta-lactam antibiotics and inhibitors of ribosome function

It is generally assumed that only actively growing bacteria are killed by inhibitors of peptidoglycan synthesis. Several exceptional examples are described here. As expected, ampicillin did not lyse nongrowing, amino acid-deprived cultures of relA+ strains of Escherichia coli, but the subsequent addition of several ribosome inhibitors (chloramphenicol, tetracycline, gentamicin, and kanamycin) caused various degrees of lysis in such ampicillin-treated cultures. Of the antibiotics tested, only streptomycin was ineffective in this regard. Peptidoglycan synthesis has been shown to be inhibited in amino acid-deprived relA+ bacteria by the stringent control mechanism (E. E. Ishiguro and W. D. Ramey, J. Bacteriol. 127:1119-1126, 1976), and the ribosome inhibitors tested here relaxed peptidoglycan synthesis to various degrees under these conditions. The relative lysis-inducing activities of the ribosome inhibitors on ampicillin-treated, amino acid-deprived bacteria were directly correlated to their relative activities as stringent control antagonists. This phenomenon was not dependent on amino acid deprivation. Cultures treated with growth inhibitory levels of the various ribosome inhibitors alone were lysed by ampicillin, apparently because peptidoglycan synthesis continues uninhibited when growth is arrested by treatment with ribosome inhibitors. These results indicate that autolysis can be triggered by the inhibition of peptidoglycan synthesis occurring in the absence of wall expansion; i.e., active cell growth is unnecessary.