Resistance mechanisms influx-efflux

Resistance is widespread and often is indncible. The three main resistance mechanisms are (1) decreased accumulation of tetracycline (decreased antibiotic influx or acquisition of an energy-dependent efflux pathway) (2) production of a ribosomal protein that displaces tetracycline from its target, a protection that also may occur by mutation and (3) enzymatic inactivation of tetracyclines. Cross-resistance amongst tetracyclines depends on which mechanism is operative. Tetracycline resistance due to a ribosomal protection mechanism produces cross-resistance to doxycycUne and minocycline because the target site protected is the same for all tetracyclines. 

Drug resistance in vitro and probably in vivo results both from inhibition of influx of the vinca alkaloids and, perhaps more frequently, from promotion of their efflux out of cells (34,35). Until relatively recently, the former mechanism was thought to predominate, and, indeed, certain acquired drug-resistant states are clearly associated with the loss of membrane proteins which can be shown to bind and transport agents into cells (34). However, other resistant states have been shown to be associated with the acquisition of membrane transport proteins which remove toxins (and, therefore, chemotherapeutic agents) both from normal and malignant cells. 

Three mechanisms of resistance to tetracycline have been described (1) decreased intracellular accumulation due to either impaired influx or increased efflux by an active transport protein pump (2) ribosome protection due to production of proteins that interfere with tetracycline binding to the ribosome and (3) enzymatic inactivation of tetracyclines. The most important of these is production... 

These results should not be construed to mean that DNA repair is the only mechanism of cisplatin resistance. There is evidence that relative amounts of glutathione are increased in cisplatin-resistant cells.Glutathione presumably uses its thiol moiety to coordinate platinum and diminish the amount that can bind to DNA. Reduced influx or increased efflux of a drug constitutes additional mechanisms by which cells become resistant. Further studies are required to ascertain which of these possibilities is most important for the cisplatin resistance phenomenon. 

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