Target site-based resistance

Target-site resistance of biotypes to ACCase inhibitors has up to now been confirmed for quite a few grass weed species of economic importance. The earliest cases of target-site based resistance were reported for biotypes of LoUum multi-Jlorum from Oregon, USA [30] and of LoUum rigidum from Australia [31]. 

Biotypes with target-site-based resistance to ACCase inhibitors were also selected in wild oat species [Avena fatua, A. sterilis). The resistance patterns were found to be variable. For example, the resistance factors for ACCase from the Canadian A. fatua biotype UMl were 105 for sethoxydim, 10 for tralkoxydim, and 10 for didofop and fenoxaprop, whereas for the Aoena fatua biotype UM33 from Canada the ratios were 10.5 for fenoxaprop, 1.2 for diclofop, 5 for sethoxydim and 1.7 for tralkoxydim. It was proposed that this was due to different point mutations, each being assodated with a characteristic resistance pattern [37]. Another reason could be the frequency of homozygote and heterozygote resistant and susceptible plants within a tested population. 

Recently PCR amplification and sequendng of plastidic ACCase domains involved in herbicide resistance has been employed to screen a spectrum of 29 grass spedes for target-site-based resistance to ACCase inhibitors by direct comparison of the sequences of plastidic ACCase around the critical codons [48]. The authors found that, in Poa annua and Festuca rubra, a leudne residue occurred at position 1781, while the wild types of all other grass spedes had an isoleucine in this position. Poa annua and F. rubra are already known from enzyme inhibition tests to possess a plastidic ACCase that is markedly less susceptible to ACCase inhibitors than the ACCase of other grass species. Thus, the leucine in position... 

The imidazolinone herbicides (Table 2.3.1) are a family of six compounds that were discovered and developed by American Cyanamid Corporation. Readers may obtain comprehensive and detailed information in The Imidazolinone Herbicides [1], a book authored by the researchers who discovered and developed the herbicides. The herbicides as a class are broad spectrum and are active both pre-and postemergence. Imidazolinones are absorbed and moved through both xylem and phloem, eventually accumulating in the meristematic tissue. Activity is characterized by rapid cessation of growth followed by plant death days or weeks after treatment. Selectivity is based most often on metabolic inactivation except for selection-developed target site based resistance. 

Because the MET-I acariddes share the same mode of action, a reasonable expectation would be that target site resistance may play a role in some of the cases where cross-resistance between MET-I acaricides has been observed. Perhaps, however, due to the complexity of the MET-I site with its many components originating from both mitochondrial and nuclear sources, target site-based resistance does not yet appear to be a primary resistance mechanism. Available information suggests that other resistance mechanisms such as metabolism predominate. As noted above, the MET-I acaricides are primarily metabolized by monooxygenases. 

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). 

Bacterial resistance can be caused by actively pumping antibiotics out of the cell and therefore decreasing the concentration at the target site. Drug efflux systems in bacteria are classified into four major groups based on their sequence homologies and functional similarities (Table 3). 

Resistance to DDT has been developed in many insect species. Although there are some cases of metabolic resistance (e.g., strains high in DDT dehydrochlorinase activity), particular interest has been focused on kdr and super kdr mechanisms based upon aberrant forms of the sodium channel—the principal target for DDT. There are many examples of insects developing resistance to dieldrin. The best-known mechanism is the production of mutant forms of the target site (GABA receptor), which are insensitive to the insecticide. 

Devine, M.D. and C.V. Eberlein (1997). Physiological, biochemical and molecular aspects of herbicide resistance based on altered target sites, pp. 295-348. In Roe, R.M. J.D. Burton, and R.J. Kuhr, eds., Herbicide Activity Toxicology, Biochemistry and Molecular Biology. Amsterdam, The Netherlands I. O. S. Press, Inc. 

Canada Pest Management Regulatory Agency, Regulatory Directive (October 6, 1999). DIR 99-06. Voluntary Pesticide Resistance -Management Labeling Based on Target Site/Mode of Action. 

US Federal Register Notice (May 10, 2000 Vol. 65, No. 91, p. 30115-30117). Pesticides Draft Guidance for Pesticide Registrants on Voluntary Pesticide Resistance Management Labeling Based on Mode/Target Site of Action on the Pest. 

In both bacteria and eucarya the susceptibility to certain ribosome-targeted inhibitors correlates with specific primary structural features of rR24A, or with features of the ribosomal domain that acts as the antibiotic binding sites. Firstly, resistance to specific ribosome-directed drugs is conferred by single-base changes within phylogenetically... 

In the presence of a continued selection pressure, metabolic resistance may facilitate the evolution of other defenses such as target site resistance, reported for the OPs and carbamates 6 and 10 years after metabolic resistance. Target site resistance to OPs and carbamates resides in modified forms of acetyl-cholinesterases (AChEs) with reduced affinity for the insecticides. AChE-based target site resistance does not necessarily confer cross resistance to all other OPs and carbamates and may be unstable in the absence of a selection pressure. 

Cases analyzed to date show that herbicide resistance is very frequently based on a target-site mutation. Within the past 35 years weed species have developed target-site resistance to most known herbicide chemistries. Those of major importance are discussed below. 

---