TmRNA Decreases the Bactericidal Activity of Aminoglycosides and the Susceptibility to Inhibitors of Cell Wall Synthesis

Abstract

trans-translation is a process that recycles ribosomes stalled on problematic mRNAs. tmRNA, coded by the ssrA gene, is a major component of trans-translation. Bacteria lacking tmRNA are more sensitive to several inhibitors of protein synthesis when compared to a wild type strain. We measured bacterial growth of the _ssrA and wild type strains in Escherichia coli in the presence of 14 antibiotics including some that do not target protein synthesis. Both the optical density of the bacterial cultures and the number of viable cells were monitored. For the ribosome-targeted antibiotics, sensitization was observed on erythromycin, chloramphenicol, kanamycin, puromycin and streptomycin. Minor or no effects were observed with clindamycin, tetracycline and spectinomycin. Surprisingly, the _ssrA strain is more sensitive than wild type to inhibitors of cell wall synthesis: fosfomycin and ampicillin. No growth difference was observed on drugs with other target sites: ofloxacin, norfloxacin, rifampicin and trimethoprim. Sensitization to antibiotics having target sites other than the ribosome suggests that trans-translation could influence antibiotic-induced stress responses. In trans-translation deficient bacteria, cell death is significantly enhanced by the two aminoglycosides that induce translational misreading, streptomycin and kanamycin.