Efflux proteins chloramphenicol

Three ofher mechanisms of chloramphenicol resisfance have been described. Firsf, a fransposon-encoded chloramphenicol efflux protein has been idenfified in E. coli. Second, some bacterial sfrains have been found to possess drug-resisfanf ribosomes, and fhird, low level resisfance can arise by chromosomal mufafions which reduce fhe amounf ofporins and fherefore impair uptake. This last mechanism is essentially that described for the AG AC antibiotics. 

Chloramphenicol inhibits protein synthesis by binding the 50S ribosomal subunit and preventing the peptidyltransferase step. Decreased outer-membrane permeability and active efflux have been identified in Gram-negative bacteria however, the major resistance mechanism is drug inactivation by chloramphenicol acetyltransferase. This occurs in... 

Clindamycin binds exclusively to the 50S subunit of bacterial ribosomes and suppresses protein synthesis. Although clindamycin, erythromycin, and chloramphenicol are not structurally related, they act at sites in close proximity, and binding by one of these antibiotics to the ribosome may inhibit the interaction of the others. There are no clinical indications for the concurrent use of these antibiotics. Macrolide resistance due to ribosomal methylation by encoded enzymes also may produce resistance to clindamycin. However, because cUndamycin does not induce the methylase, there is cross-resistance only if the enzyme is produced con-stitutively. Clindamycin is not a substrate for macrolide efflux pumps thus, strains that are resistant to macrolides by this mechanism are susceptible to clindamycin. Altered metabolism occasionally causes clindamycin resistance. 

Selective toxicity of these protein synthesis inhibitors against microorganisms may be explained by target differences. Chloramphenicol does not bind to the SOS ribosomal RNA of mammalian cells, though it can inhibit the functions of mitochotidrial ribosomes, which contain 70S ribosomal RNA. Tetracyclines have little effect on mammalian protein synthesis because an active efflux mechanism prevents their intracellular accumulation. 

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