Resistance to ALS inhibitors

Foes et al. (1998) reported that a common waterhemp biotype not controlled by triazine or ALS-inhibiting herbicides was isolated from a field in Illinois in the fall of 1996. Patzoldt et al. (2004, 2005) have reported on a tall waterhemp biotype in Illinois that has multiple resistance to ALS inhibitors, PPO inhibitors, and atrazine in the same plants. Maertens et al. (2004) reported a smooth pigweed biotype from southern Illinois confirming multiple resistance to both atrazine and ALS inhibitors. 

Triazine-resistant weeds have been controlled successfully in many countries by the use of alternative herbicides often in combination with atrazine, but the number of weed species resistant to ALS-inhibitor herbicides now greatly exceeds the triazine-resistant species and is increasing much faster. By combining the Heap (2006) survey with Dr. LeBaron s global survey and a review of the literature, we find that there are at present 108 weed species with biotypes resistant to ALS inhibitors, including 70 dicotyledonous and 38 monocotyledonous weeds in 19 countries. 

Numerous cases of resistance to the ALS inhibitors have now been reported in other broadleaf weed species, including pigweed and cocklebur, as well as grasses such as shattercane. Walsh et al. (2001) reported that only a few years after the first case of ALS-resistant wild radish, a major weed in Australian wheat fields, 21% of randomly collected wild radish populations were found to be resistant to chlorsulfuron. Patzoldt and Tranel (2002) reported that cloransulam resistance was found in an Indiana population of giant ragweed during the first year of that herbicide s commercialization in 1998, and that the resistant plants were cross-resistant to imazethapyr and chlorimuron. Since 1989, the number of species resistant to ALS inhibitors has increased almost 10-fold in crops and on roadsides. The total ALS-resistant weed species now number 108, as seen in Tables 11.4a and b). 

Christopher et al. (1992) reported that a chlorsulfuron-resistant rigid ryegrass in Australia was resistant to most other sulfonylurea and imidazolinone ALS inhibitors. However, a common cocklebur biotype resistant to several imida-zolinone herbicides was not resistant to sulfonylurea herbicides (Saari et al., 1994). It is, therefore, difficult to generalize as to patterns of resistance within the five classes of ALS inhibitors. Weed biotypes resistant to one herbicide will usually show some level of resistance to most herbicides within the same class, and may in addition show some resistance to ALS inhibitors in other classes. 

In 1987, Moss first reported that a blackgrass biotype resistant to chlorotoluron and isoproturon (urea herbicides in WSSA Group 7) was also resistant to the ALS inhibitor chlorsulfuron. Menendez el al. (1997) also found that a chlorotoluron-resistant blackgrass biotype in Spain was resistant to ALS inhibitors (e.g., chlorsulfuron and imaza-methabenz), and that the resistance was due to its greater ability to metabolize the herbicides. 

Ferguson et al. (2001) confirmed resistance to ALS inhibitors (imazethapyr or flumetsulam) in populations of Powell amaranth and redroot pigweed in Ontario. High-level cross-resistance to thifensulfuron was found in two populations of each species. On the other hand, Poston et al. (2001) found that a population of imidazolinone-resistant smooth pigweed was 10-fold more sensitive to cloransulam-methyl (another class of ALS inhibitors) than the sensitive population. 

Shaner, D. L., Heap, I. Herbicide Resistance in North America The Case for Resistance to ALS Inhibitors in the United States in Agrochemical Resistance, ACS Symposium Series,... 

Straight arrows indicate resistance to ALS inhibitors, and dotted arrows do ressitance. 

Kasai T, Iwanaga Y, Iha H et al. Prevalent loss of mitotic spindle checkpoint in adult T-cell leukemia confers resistance to microtubule inhibitors. JBiol Chem 2002 277 5187-5193. 

Byrnes VW, Sardana VV, Schleif WA, Condra JH, Waterbury JA, Wolfgang JA, et al.. Comprehensive mutant enzyme and viral variant assessment of human immunodeficiency virus type 1 reverse transcriptase resistance to nonnucleoside inhibitors. Antimicrob Agents Chemother 1993 37 1576-1579. 

Goldman ME, O Brien JA, Ruffing TL, Schleif WA, Sardana VV, Bynes VW, et al. A nonnucleoside reverse transcriptase inhibitor active on human immunodeficiency type 1 isolates resistant to related inhibitors. Antimicrob Agents Chemother 1993 37 947-949. 

Long J, Parkin B, Ouillette P et al (2010) Multiple distinct molecular mechanisms influence sensitivity and resistance to MDM2 inhibitors in adult acute myelogenous leukemia. Blood 116 71-80... 

Kohl TM, Hellinger C, Ahmed F et al (2007) BH3 mimetic ABT-737 neutralizes resistance to FLT3 inhibitor treatment mediated by FLT3-independent expression of BCL2 in primary AML blasts. Leukemia 21 1763-1772... 

Mellors JW, Dutschman GE, Im GJ, et al. In vitro selection and molecular characterization of human immunodeficiency virus-1 resistant to nonnucleoside inhibitors of reverse transcriptase. Mol Pharmacol 1992 41 446-451. 

Resistant biotypes being reported in the early 1990s were selected by chlorsul-furon or metsulfuron-methyl in wheat-growing areas or by sulfometuron-methyl in non-crop areas. While resistance of Lolium rigidum to ALS-inhibitors was attributed to enhanced herbicide metabolism [50] it was shown, for Lolium perenne and dicotyledonous species like Stellaria media, Kochia scoparia, Scdsola iberica and Lactuca serriola, that resistant biotypes had a mutated ALS with reduced susceptibility to ALS-inhibitmg herbicides [51-53]. The IC50S for sulfonylureas, which were determined in vitro with ALS isolated from Stellaria media, Salsola iberica and Lolium perenne, increased 4- to 50-fold in the resistant biotypes. Smaller increases, about 2- to 7-fold, were determined in the same biotypes for the imidazo-linone herbicide imazapyr [53]. 

Strain development is crucial for viability of fermentative butanol production. Approaches targeting individual genes, enzymes or pathways can be used, but also approaches at global and system levels are more effective for stress tolerance improvement to improve butanol titre. There are three priority directions for strain development improvement of butanol tolerance, increased butanol production and utilisation of cheap feedstock (utilisation of various monosaccharides and resistance to microbial inhibitors). Clostridia have potential as a commercial strain, but heterologous hosts might prove advantageous, due to the homofermentative pathway (Branduardi et al. 2014 Xue et al. 2013a). 

Altogether, these studies show that, albeit much less characterized yet than pathogen microbiota, LAB biofilms occur in the food chain in which they may have dual beneficial and detrimental properties. Similarly to pathogen biofilms, LAB biofilms show increased resistance to environmental stresses than their planktonic counterparts. This applies to resistance to different inhibitors and preservatives such as organic acids (namely, acetic acid, citric acid, lactic acid, and malic acid) and ethanol used in the food industry (Kubota et al. 2008,2009). This also applies to resistance to sanitizers used for equipment cleaning in the food industry (Somers et al. 2001). Given that LAB may face... 

Viruses that contain amino acid substitutions in the sialidase that impart resistance to the developed inhibitors have been isolated from serial passage of virus in the presence of drug in cell culture and from the clinical setting (reviewed in McKimm-Breschkin 2000 Zambon and Hayden 2001 Cinatl et al. 2007a Reece 2007). In addition, influenza B virus variants with reduced drug sensitivity have been isolated from previously untreated patients (Hurt et al. 2006 Hatakeyama et al. 2007). The types of mutations that are observed are sub-type specific. The mutations present in variants isolated from clinical samples are shown in Table 1, and their locations within the sialidase active site are shown diagrammatically in Fig. 9. 

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