Regulation of ribosome phosphorylation and antibiotic sensitivity in Tetrahymena thermophila: A correlation

Tetrahymena thermophila cells transferred from growth medium into a dilute salt (starvation) medium shortly (approximately 6-8 hrs) become more resistant to the in vivo inhibitory effects of the antibiotics cycloheximide, tetracycline and emetine. They also be come more sensitive to the inhibitory effects of paromomycin and anisomycin. By comparing ribosomes from growing and starved cells we have found that for at least two of these drugs differences between growing cell and starved cell ribosomes exist with respect to drug-ribosome interactions. In addition, we found that isolated monosomic ribosomes from starved cells are more resistant to thermal denaturation than are monosomic ribosomes from growing cells. The kinetics of all these changes following transfer of growing cells to starvation medium is the same and correlates with a change in the extent of phosphorylation of a single small subunit ribosomal protein. As judged by our in vitro assays, enzymatic removal of this phosphate converts "starved cell" ribosomes into "growing cell" ribosomes. We have extended these studies to show that the phenomenon of drug adaptation in Tetrahymena, at least with respect to cycloheximide, is associated with this ribosome phosphorylation.