1887

Abstract

The unusual sensitivity of a isolate to three inhibitors of prokaryote protein synthesis [tetracycline (TET), chloramphenicol (CAM), erythromycin (ERY)] was investigated. TET inhibited growth in shake culture by 40% at 10 g ml and 99% at 100 g ml within 5 h (one doubling period). CAM inhibited growth by 40% at 500 g ml and 70%, at 1 mg ml. Cycloheximide (CHI), a eukaryote protein synthesis inhibitor, blocked growth completely at 1 g ml. These agents reduced incorporation of leucine and phenylalanine into protein by 40 to 50% (100 g TET ml, 500 g CAM ml) or 93% (1 g CHI ml) within 20 min. This rapid inhibitory effect could not be attributed to impaired mitochondrial energy generation. TET inhibition increased to 90% by 60 min, but CAM inhibition did not change for 5 h. TET inhibited both the transport and protein synthetic (cytoplasmic) components of amino acid incorporation, but CAM impaired only the transport activity. CHI blocked protein synthesis, but did not inhibit transport de-tectably. In contrast to these results, growth inhibition by ERY did not increase with dose (40% inhibition at 10 to 500 g ml), and ERY at 500 g ml inhibited neither amino acid transport nor protein synthesis in 5 h. The results indicate that the sensitivity of P. to these prokaryote inhibitors reflects unusual permeability properties, which account for impaired transport (CAM, TET) and allow access of the drugs to sensitive intracellular sites, the cytoplasmic (TET) and mitochondrial (ERY) protein synthetic systems.

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1978-09-01
2024-12-14
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