Sequestration resistance mechanisms

As a consequence of, or perhaps in spite of, metal toxicity, some microorganisms have developed various resistance mechanisms to prevent metal toxicity. The strategies are either to prevent entry of the metal into the cell or actively to pump the metal out of the cell. This can be accomplished by either sequestration, active transport or chemical transformation through metal oxidation or reduction. 

Sequestration in insects This is another resistance mechanism in which GSTs were found to be involved in pyrethroid resistance. Kostaropoulos et al. (2001) have reported that GST confers protection against deltamethrin by binding to the insecticide in the yellow mealworm ijenebrio monitor). 

Intensive use of the herbicide paraquat has resulted in the evolution of resistance in various weed species. Intensive research on the resistance mechanisms was mainly carried out with resistant biotypes from Hordeum spp. and Conyza spp., and altered distribution of the herbicide in the resistant weeds was suggested as the cause - or at least the partial cause - of resistance. In resistant Conyza canadensis it was supposed that a paraquat inducible protein may function by carrying paraquat to a metabolically inactive compartment, either the cell wall or the vacuole. This sequestration process would prevent the herbicide from getting in sufficient amounts into the chloroplasts as the cellular site of paraquat action. Inhibitors of membrane transport systems, e.g., N,N-dicyclohexylcarbodii-mide (DCCD), caused a delay in the recovery of photosynthetic functions of the paraquat-resistant biotype, when given after the herbicide. These transport inhibitor experiments supported the involvement of a membrane transporter in paraquat resistance [75]. 

There are a number of different mechanisms by which microorganisms resist metal toxicity (Table 11.1). Five mechanisms that microbes use to mediate metal toxicity have been proposed and they include (1) formation of a permeability barrier,21-24 (2) active transport,25-29 (3) sequestration,30-32 (4) enzymatic detoxification,33 34 and (5) reduction in sensitivity.35,36 Microbes may use one or more of these mechanisms to exclude nonessential metals and regulate internal concentrations of essential metals. 

Antibiotic resistance can be the result of several molecular mechanisms (Table 1). Some of the most important of these mechanisms include enzyme-catalyzed antibiotic inactivation or modification, altered transport such as efflux, and others such as metabolic bypass and sequestration. Each of these mechanisms requires the synthesis of associated proteins to mediate resistance. These are often highly specialized and efficient, and frequently the corresponding genes can be acquired on mobile... 

Ouar, Z. Lacave, R. Bens, M. VandewaUe, A. Mechanisms of altered sequestration and efflux of chemotherapeutic drugs by multidrug-resistant cells. Cell Biol. Toxicol. 1999, 15 91-100. 

Our current understanding of insecticide resistance phenomena in insects and other arthropods is based upon genetic and biochemical evidence, which implicates a number of different mechanisms (1). These include metabolic mechanisms, which result in enhanced rates of insecticide detoxication or sequestration of insecticide, and also mechanisms involving reduced... 

While most plants are susceptible to paraquat, some paraquat-resistant horseweed (Erigeron sp. and Conyza sp.) biotypes are apparently insensitive to the herbicide due either to elevated levels of superoxide dismutase and other enzymes in a pathway detoxifying oxygen radicals or to differential sequestration of paraquat in the weed (8, 9). Data on the mechanism of most other types of herbicide resistance in weeds are still not complete. 

Nontarget-site resistance is caused by mechanisms that reduce the amount of herbicidally active compound reaching the target site. An important mechanism is enhanced metabolic detoxification of the herbicide in the weed, with the effect that only insufficient amounts of herbicidally active substance will reach the target site. Furthermore, reduced uptake and translocation or sequestration of the herbicide may lead to insufficient herbicide transport to the target site. 

The underlying mechanism of this inhibition appears to be the sequestration of undecaprenyl pyrophosphate by bacitracin in the presence of a divalent cation and not the binding of the antibiotic to an enzyme (Stone and Strominger, 1971). Drug resistance in this case is related to elevated levels of undecaprenyl derivatives, rather than to a mutant enzyme in the undecaprenyl phosphate cycle. 

Many different mechanisms to mediate heavy metal resistance in prokaryotes exist, and have been carefully reviewed elsewhere (Ralston and O Halloran 1990 O Halloran 1993). In eukaryotes, this job is done by metallothioneins which sequester heavy metal ions and make them unavailable to exert toxic effects (reviewed by Hamer 1986 Andrews 1990). In this regard, heme-hepoxin induces both heme oxygenase and MT expression in human promyelocytic leukaemia cells and mouse hepatoma cells (Alam et al. 1989). The authors suggest that MT may sequester the nontoxic metal zinc, which would otherwise compete with Fe for occupation of sites on Fe-dependent regulatory proteins such as the IRE-BP. Thus, it is possible that sequestration of metals by MT could mediate, not only the direct toxic effect of such metals (reviewed in Chap. 1, this volume), but... 

---