Multiple resistance mechanisms

Multiple-resistance mechanisms, defined as resistance due to more than one mode of action or class of herbicide, have been reported in several ALS-resistant weed biotypes - including false cleavers, wild oat, common waterhemp, kochia, rigid ryegrass in Australia (Powles and Matthews, 1992 Preston and Mallory-Smith, 2001), and wild radish (Walsh etal, 2004a). 

One obvious way to treat pathogens that have accumulated multiple resistance mechanisms or are intrinsically resistant to a given therapy is to use a drug with an entirely different mode of action. Since the major antifungal therapies target sterol biosynthesis or composition, a large variety of additional metabolic pathways are theoretically available. In reality,... 

Mann, P.A., and Perlin, D.S. (2003) Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrobial Agents and Chemotherapy, 47, 1719-1726. 

Acquired resistance has been observed by constitutive upregulation of mdr efflux pump expression due to a mutation inactivating a respective repressor or inducibly, caused by molecules transiently inactivating repressor molecules upon binding. Depending upon the substrate spectra of the respective subset of efflux pumps upregulated, a multiple drug resistance (mdr) phenotype is expressed, which in combination with a specific resistance mechanism can contribute to a clinically relevant level of resistance. 

G.D. Albertson, M. Niimi, R.D. Cannon, and H.F. Jenkinson, Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance, Antimicrob. Agents Chemother., 40, 2835, 1996. 

Multiple-resistance is when more than one mechanism conferring resistance to herbicides in different chemical classes is active in an individual weed or population of weeds. Plants with multiple resistance may possess two or more distinct resistance mechanisms. Two grass species that display both cross- and multiple-resistance are rigid (or annual) ryegrass and blackgrass (Hall et al., 1994). 

Hall, L.M., J.A.M. Holtum, and S.B. Powles (1994). Mechanisms responsible for cross resistance and multiple resistance. In S.B. Powles and J.A.M. Holtum, eds., Herbicide Resistance in Plants Biology and Biochemistry. Boca Raton, Florida CRC Press, pp. 243-261. 

Hall et al. (1998) reported that an ALS-resistant biotype of false cleavers was cross-resistant to a broad range of ALS inhibitors, as well as to an auxin-type herbicide, quinclorac, which had never before been applied to these fields. A similar case of quinclorac multiple resistance in smooth crabgrass has been reported in California when plants were previously treated with ACCase herbicides. Data suggest a target site-based mechanism of resistance involving the accumulation of cyanide derived from stimulated ACC synthesis, which is a precursor of ethylene (Abdallah et al., 2004). 

Rituximab is a chimeric antibody that contains the human IgGx constant region and murine variable region, and binds the membrane-associated human CD20 antigen. Evidence for multiple mechanisms of rituximab action has been reported [96, 97]. Rituximab can deplete CD20-positive B cells via ADCC, CDC, or apoptosis however, it is not clear which is the most important mechanism in humans. Resistance to rituximab s in-vivo effects has been reported, but the underlying resistance mechanisms are not well understood. 

Cross-resistance is not the same as multiple resistance. Multiple resistance may occur when a population of insects comes into contact with two or more different insecticides. Thus, cross-resistance refers to those cases in which a single defense mechanism confers resistance against various insecticides, whereas multiple resistance refers to cases of resistance to various insecticides conferred by different mechanisms. In general, multiple resistance is due to the sequential selection of populations with replacement insecticides. Each new insecticide selects one or more mechanisms of resistance, and each mechanism usually confers cross-resistance to several other insecticides (Georghiou and Taylor, 1976). Table 10.8 shows the multiple resistance to organophosphate, carbamate, and organochlo-rine insecticides in two strains of Culex pipiens quinquefasciatus. 

Figure 2 Integrons, transposons, and R-plasmids often collect multiple antibiotic resistance genes. As a result, selection of one resistance mechanism coselects for resistance to additional resistance genes. The scheme shows a typical arrangement for an integron with associated integrase-encoding gene (int), a promoter to drive gene transcription (P), and antibiotic resistance elements (A- ).

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