tmRNA (also known as SsrA or 10Sa RNA) is involved in a
trans-translation reaction that contributes to the
recycling of stalled ribosomes at the 3′ end of an mRNA
lacking a stop codon or at an internal mRNA cluster of rare
codons. Inactivation of the ssrA gene in most bacteria
results in viable cells bearing subtle phenotypes, such as
temperature-sensitive growth. Herein, we report on the functional
characterization of the ssrA gene in the cyanobacterium
Synechocystis sp. strain PCC6803. Deletion of the
ssrA gene in Synechocystis resulted in viable
cells with a growth rate identical to wild-type cells. However,
null ssrA cells (ΔssrA) were not viable
in the presence of the protein synthesis inhibitors
chloramphenicol, lincomycin, spiramycin, tylosin, erythromycin,
and spectinomycin at low doses that do not significantly affect
the growth of wild-type cells. Sensitivity of ΔssrA
cells similar to wild-type cells was observed with kasugamycin,
fusidic acid, thiostrepton, and puromycin. Antibiotics unrelated
to protein synthesis, such as ampicillin or rifampicin, had
no differential effect on the ΔssrA strain.
Furthermore, deletion of the ssrA gene is sufficient
to impair global protein synthesis when chloramphenicol is added
at sublethal concentrations for the wild-type strain. These
results indicate that ribosomes stalled by some protein synthesis
inhibitors can be recycled by tmRNA. In addition, this suggests
that the first elongation cycle with tmRNA, which incorporates
a noncoded alanine on the growing peptide chain, may have
mechanistic differences with the normal elongation cycles that
bypasses the block produced by these specific antibiotics. tmRNA
inactivation could be an useful therapeutic target to increase
the sensitivity of pathogenic bacteria against antibiotics.