Cycloheximide resistance

According to Siegal and Sisler, cycloheximide resistance is due to an alteration in ribosomal protein. A mutation in the respective structural gene(s) of the nonsense or frameshift type most certainly will lead to the formation of a completely nonfunctional protein which will be lethal. Therefore, only missense or very terminal nonsense or frameshift mutations can be expected to lead to the formation of a functional protein which causes resistance against cycloheximide. ICR-170 is considered to be a frameshift mutagen, and consequently it is not able to induce the required type of mutation. 

There are several reasons for believing that mitochondrial protein synthesis is functional in the Ml26 mutant (1) Significant chloramphenicol, acriflavin, and ethidium bromide sensitivity of amino acid incorporations have been detected in vivo in the mutant. The relative extent of these inhibitions is only 20% of the cycloheximide-resistant counts because of the high cycloheximide resistance of S. pombe. It must be noted, however, that the absolute extent of these inhibitions is in the range expected for mitochondrial protein synthesis and is similar to that of the wild type (about 5% of the total cellular amino acid incorporation). (2) Cytochrome feggo, which was reported to be synthesized on mitochondrial... 

The data of Table II provide additional information about the subunits. The precursor pool sizes of the three mitochondrially synthesized cytochrome oxidase subunits differ markedly, being 2% for the 20,000 Mr subunit, 5% for the 28,000 Mr subunit, and 10% for the 36,000 Mr subunit. Hence, in the presence of cycloheximide, the assembly of cytochrome oxidase continues only for a limited period of time, i.e., until the smallest cytoplasmic precursor pool is exhausted. The amount of label which appears in the holoenzyme after this period of time decreases as the size of the precursor pool to be passed increases. This fact explains why in the presence of cycloheximide, less radioactivity appeared in the 28,000 Mr and 36,000 Mr subunits than in the 20,000 Mr subunit (Fig. 7B). However, when cycloheximide is removed, the assembly of the holoenzyme recommences, and all of the H-labeled polypeptides can be integrated. In this manner, a higher cycloheximide-resistant radioactive labeling of the 28,000 Mr and the 36,000 Mr subunits of cytochrome oxidase is obtained with N. crassa. ... 

Onychomycosis Caused by Scopulariopsis brevicaulis. S. brevicaulis is the most common cause of onychomycosis by molds, presenting with a cinnamon discoloration of the toenails. Direct examination reveals the distinctive, lemonshaped conidia taking up Parker s stain quickly. On agar with cycloheximide the partially resistant fungus grows slowly. Therapy is problematic, local therapy may be tried after removal. 

In addition to the ABC transporters, the MFS family transporters play an important role in clinical drug resistance [161]. The most prominent ones are Mdrl ]162, 163] and Flul ]164]. CaMDRl, formerly known as BEN confers resistance to a variety of different compounds. Cells lacking CaMDRl are susceptible to 4-nitro-quinoline-N-oxide, methotrexate, and cycloheximide ]165, 166]. The closest yeast homologue of CaMDRl is PLRl. As mentioned above, Flrl is known to be involved in drug transport and it mediates resistance to the same spectrum of drugs as CaMDRl. 

Reflecting the bacterial ancestry of mitochondria, mitochondrial ribosomes resemble bacterial ribosomes and differ from eukaryotic cytosolic ribosomes in their RNA and protein compositions, their size, and their sensitivity to certain antibiotics (see Figure 4-24). For instance, chloramphenicol blocks protein synthesis by bacterial and mitochondrial ribosomes from most organisms, but cycloheximide does not. This sensitivity of mitochondrial ribosomes to the important aminoglycoside class of antibiotics is the main cause of the toxicity that these antibiotics can cause. Conversely, cytosolic ribosomes are sensitive to cycloheximide and resistant to chloramphenicol. In cultured mammalian cells the only proteins synthesized in the presence of cycloheximide are encoded by mtDNA and produced by mitochondrial ribosomes. I... 

Mitochondrial ribosomes resemble bacterial ribosomes in their structure, sensitivity to chloramphenicol, and resistance to cycloheximide. 

The phenotype characteristics of T. thermophila strain BI3840 are amicronucleated (amc), pigment producing (pig), and resistant to 25pg/mL of cycloheximide (cy-r)... 

Indeed, the amount of the chloramphenicol-resistant incorporation of PHjleucine into cytochrome b was slightly increased after washing out of the chloramphenicol and after further growth of the cells (Figs. 16C and 17C). Furthermore, the asymmetric distribution of radioactivity over the radioactivity peak (Fig. 17B), which is always observed upon gel electrophoresis of cytochrome b from the cycloheximide-treated cells, may... 

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