scholarly journals A Review of Current Knowledge of Resistance Aspects for the Next-Generation Succinate Dehydrogenase Inhibitor Fungicides

2013 ◽  
Vol 103 (9) ◽  
pp. 880-887 ◽  
Author(s):  
Helge Sierotzki ◽  
Gabriel Scalliet
Keyword(s):  
Succinate Dehydrogenase ◽  
Mode Of Action ◽  
Fungal Pathogens ◽  
Current Knowledge ◽  
Field Performance ◽  
Population Level ◽  
Tca Cycle ◽  
Cross Resistance ◽  
Docking Simulations ◽  
Succinate Dehydrogenase Inhibitor

The new broad-spectrum fungicides from the succinate dehydrogenase inhibitor (SDHI) class have been quickly adopted by the market, which may lead to a high selection pressure on various pathogens. Cases of resistance have been observed in 14 fungal pathogens to date and are caused by different mutations in genes encoding the molecular target of SDHIs, which is the mitochondrial succinate dehydrogenase (SDH) enzyme. All of the 17 marketed SDHI fungicides bind to the same ubiquinone binding site of the SDH enzyme. Their primary biochemical mode of action is the blockage of the TCA cycle at the level of succinate to fumarate oxidation, leading to an inhibition of respiration. Homology models and docking simulations explain binding behaviors and some peculiarities of the cross-resistance profiles displayed by different members of this class of fungicides. Furthermore, cross-resistance patterns among SDHIs is complex because many mutations confer full cross resistance while others do not. The nature of the mutations found in pathogen populations varies with species and the selection compound used but cross resistance between all SDHIs has to be assumed at the population level. In most of the cases where resistance has been reported, the frequency is still too low to impact field performance. However, the Fungicide Resistance Action Committee has developed resistance management recommendations for pathogens of different crops in order to reduce the risk for resistance development to this class of fungicides. These recommendations include preventative usage, mixture with partner fungicides active against the current pathogen population, alternation in the mode of action of products used in a spray program, and limitations in the total number of applications per season or per crop.

Activity of A Novel Succinate Dehydrogenase Inhibitor Fungicide Pydiflumetofen against Fusarium fujikuroi causing Rice Bakanae Disease

Plant Disease ◽  
2021 ◽  
Author(s):  
Yang Bai ◽  
Chun-Yan Gu ◽  
Rui Pan ◽  
Muhammad Abid ◽  
Hao-Yu Zang ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Succinate Dehydrogenase ◽  
Field Trials ◽  
Cell Membrane Permeability ◽  
Cross Resistance ◽  
Fusarium Fujikuroi ◽  
Control Efficacy ◽  
Bakanae Disease ◽  
Geographical Regions ◽  
Succinate Dehydrogenase Inhibitor

New fungicides are tools to manage fungal diseases and overcome emerging resistance in fugnal pathogens. In this study, a total of 121 isolates of Fusarium fujikuroi, the causal agent of rice bakanae disease (RBD), were collected from various geographical regions of China, and their sensitivity to a novel succinate dehydrogenase inhibitor (SDHI)fungicide ‘pydiflumetofen’ was evaluated. The 50% effective concentration (EC50) value of pydiflumetofen for mycelial growth suppression ranged from 0.0101 to 0.1012 μg/ml and for conidial germination inhibition ranged from 0.0051to 0.1082 μg/ml. Pydiflumetofen treated hyphae showed contortion and increased branching, cell membrane permeability, and glycerol content significantly. The result of electron microscope transmission indicated that pydiflumetofen damaged the mycelial cell wall and the cell membrane, and almost broken up the cells, which increased the intracellular plasma leakage. There was no cross-resistance between pydiflumetofen and the widely used fungicides such as carbendazim, prochloraz, and phenamacril. Pydiflumetofen was found safe to seeds and rice seedlings of four rice cultivars, used up to 400 μg/ml. Seed treatment significantly decreased the rate of diseased plants in the greenhouse as well as in field trials in 2017 and 2018. Pydiflumetofen showed superb results against RBD, when used at 10 or 20 g a.i./100 kg of treated seeds, providing over 90% control efficacy (the highest control efficacy was up to 97%), which was significantly higher than that of 25% phenamacril (SC) at 10g or carbendazim at 100 g. Pydiflumetofen is highly effective against F. fujikuroi growth and sporulation as well as RBD in the field.

scholarly journals Succinate dehydrogenase inhibitor (SDHI) fungicide resistance prevention strategy

2011 ◽  
Vol 64 ◽  
pp. 119-124 ◽  
Author(s):  
A.H. McKay ◽  
G.C. Hagerty ◽  
G.B. Follas ◽  
M.S. Moore ◽  
M.S. Christie ◽  
...  
Keyword(s):  
New Zealand ◽  
High Risk ◽  
Succinate Dehydrogenase ◽  
Fungicide Resistance ◽  
Fungal Pathogens ◽  
Resistance Management ◽  
Resistance Development ◽  
Development Of Resistance ◽  
Action Committee ◽  
Succinate Dehydrogenase Inhibitor

Succinate dehydrogenase inhibitor (SDHI) fungicides are currently represented in New Zealand by eight active ingredients bixafen boscalid carboxin fluaxapyroxad fluopyram isopyrazam penthiopyrad and sedaxane They are either currently registered or undergoing development in New Zealand for use against a range of ascomycete and basiodiomycete pathogens in crops including cereals ryegrass seed apples pears grapes stonefruit cucurbits and kiwifruit These fungicides are considered to have medium to high risk of resistance development and resistance management is recommended by the Fungicide Resistance Action Committee (FRAC) in Europe Guidelines are presented for use of SDHI fungicides in New Zealand to help avoid or delay the development of resistance in the fungal pathogens that they target

scholarly journals Hidden Host Plant Associations of Soilborne Fungal Pathogens: An Ecological Perspective

2013 ◽  
Vol 103 (6) ◽  
pp. 538-544 ◽  
Author(s):  
Glenna M. Malcolm ◽  
Gretchen A. Kuldau ◽  
Beth K. Gugino ◽  
María del Mar Jiménez-Gasco
Keyword(s):  
Host Plant ◽  
Population Biology ◽  
Fungal Pathogens ◽  
Current Knowledge ◽  
Vascular Plant ◽  
Disease Symptoms ◽  
Nonhost Plant ◽  
Plant Associations ◽  
Definition Of ◽  
Forest Plants

Much of the current knowledge on population biology and ecology of soilborne fungal pathogens has been derived from research based on populations recovered from plants displaying disease symptoms or soil associated with symptomatic plants. Many soilborne fungal pathogens are known to cause disease on a large number of crop plants, including a variety of important agronomical, horticultural, ornamental, and forest plants species. For instance, the fungus Verticillium dahliae causes disease on >400 host plants. From a phytopathological perspective, plants on which disease symptoms have not been yet observed are considered to be nonhosts for V. dahliae. This term may be misleading because it does not provide information regarding the nature of the plant–fungus association; that is, a nonhost plant may harbor the fungus as an endophyte. Yet, there are numerous instances in the literature where V. dahliae has been isolated from asymptomatic plants; thus, these plants should be considered hosts. In this article, we synthesize scattered research that indicates that V. dahliae, aside from being a successful and significant vascular plant pathogen, may have a cryptic biology on numerous asymptomatic plants as an endophyte. Thus, we suggest here that these endophytic associations among V. dahliae and asymptomatic plants are not unusual relationships in nature. We propose to embrace the broader ecology of many fungi by differentiating between “symptomatic hosts” as those plants in which the infection and colonization by a fungus results in disease, and “asymptomatic hosts” as those plants that harbor the fungus endophytically and are different than true nonhosts that should be used for plant species that do not interact with the given fungus. In fact, if we broaden our definition of “host plant” to include asymptomatic plants that harbor the fungus as an endophyte, it is likely that the host ranges for some soilborne fungal pathogens are much larger than previously envisioned. By ignoring the potential for soilborne fungal pathogens to display endophytic relationships, we leave gaps in our knowledge about the population biology and ecology, persistence, and spread of these fungi in agroecosystems.

Impact of genotypic diversity on selection of subtype-specific drug resistance profiles during raltegravir-based therapy in individuals infected with B and BF recombinant HIV-1 strains

2020 ◽  
Vol 75 (6) ◽  
pp. 1567-1574
Author(s):  
Daniela Sánchez ◽  
Solange Arazi Caillaud ◽  
Ines Zapiola ◽  
Silvina Fernandez Giuliano ◽  
Rosa Bologna ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Current Knowledge ◽  
Phylogenetic Analyses ◽  
Genotypic Diversity ◽  
Resistance Testing ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Middle Income ◽  
Subtype B ◽  
Hiv 1

Abstract Background Current knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate. Materials and methods HIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses. Results Of the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%), 7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping. INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs. Conclusions Alternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the use of INIs.

scholarly journals Algorithmic Methods to Infer the Evolutionary Trajectories in Cancer Progression

2015 ◽  
Author(s):  
Giulio Caravagna ◽  
Alex Graudenzi ◽  
DANIELE RAMAZZOTTI ◽  
Rebeca Sanz-Pamplona ◽  
Luca De Sano ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Current Knowledge ◽  
Population Level ◽  
Selective Advantage ◽  
Explanatory Models ◽  
Driver Mutations ◽  
Cross Sectional ◽  
Progression Model ◽  
Colorectal Cancer Progression ◽  
Ngs Data

The genomic evolution inherent to cancer relates directly to a renewed focus on the voluminous next generation sequencing (NGS) data, and machine learning for the inference of explanatory models of how the (epi)genomic events are choreographed in cancer initiation and development. However, despite the increasing availability of multiple additional -omics data, this quest has been frustrated by various theoretical and technical hurdles, mostly stemming from the dramatic heterogeneity of the disease. In this paper, we build on our recent works on "selective advantage" relation among driver mutations in cancer progression and investigate its applicability to the modeling problem at the population level. Here, we introduce PiCnIc (Pipeline for Cancer Inference), a versatile, modular and customizable pipeline to extract ensemble-level progression models from cross-sectional sequenced cancer genomes. The pipeline has many translational implications as it combines state-of-the-art techniques for sample stratification, driver selection, identification of fitness-equivalent exclusive alterations and progression model inference. We demonstrate PiCnIc's ability to reproduce much of the current knowledge on colorectal cancer progression, as well as to suggest novel experimentally verifiable hypotheses.

scholarly journals Functional succinate dehydrogenase deficiency is a common adverse feature of clear cell renal cancer

2021 ◽  
Vol 118 (39) ◽  
pp. e2106947118
Author(s):  
Ritesh K. Aggarwal ◽  
Rebecca A. Luchtel ◽  
Venkata Machha ◽  
Alexander Tischer ◽  
Yiyu Zou ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Catalytic Domain ◽  
Clear Cell ◽  
Competitive Inhibition ◽  
Hypoxia Inducible Factor ◽  
Tca Cycle ◽  
Product Inhibition ◽  
Down Regulation ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Pathogenesis

Reduced succinate dehydrogenase (SDH) activity resulting in adverse succinate accumulation was previously considered relevant only in 0.05 to 0.5% of kidney cancers associated with germline SDH mutations. Here, we sought to examine a broader role for SDH loss in kidney cancer pathogenesis/progression. We report that underexpression of SDH subunits resulting in accumulation of oncogenic succinate is a common feature in clear cell renal cell carcinoma (ccRCC) (∼80% of all kidney cancers), with a marked adverse impact on survival in ccRCC patients (n = 516). We show that SDH down-regulation is a critical brake in the TCA cycle during ccRCC pathogenesis and progression. In exploring mechanisms of SDH down-regulation in ccRCC, we report that Von Hippel-Lindau loss-induced hypoxia-inducible factor–dependent up-regulation of miR-210 causes direct inhibition of the SDHD transcript. Moreover, shallow deletion of SDHB occurs in ∼20% of ccRCC. We then demonstrate that SDH loss-induced succinate accumulation contributes to adverse loss of 5-hydroxymethylcytosine, gain of 5-methylcytosine, and enhanced invasiveness in ccRCC via inhibition of ten-eleven translocation (TET)-2 activity. Intriguingly, binding affinity between the catalytic domain of recombinant TET-2 and succinate was found to be very low, suggesting that the mechanism of succinate-induced attenuation of TET-2 activity is likely via product inhibition rather than competitive inhibition. Finally, exogenous ascorbic acid, a TET-activating demethylating agent, led to reversal of the above oncogenic effects of succinate in ccRCC cells. Collectively, our study demonstrates that functional SDH deficiency is a common adverse feature of ccRCC and not just limited to the kidney cancers associated with germline SDH mutations.

Fusarium graminearum FgSdhC1 point mutation A78V confers resistance to the succinate dehydrogenase inhibitor pydiflumetofen

2022 ◽  
Author(s):  
Wenyong Shao ◽  
Jingrui Wang ◽  
Huiyuan Wang ◽  
Ziyue Wen ◽  
Chao Liu ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Point Mutation ◽  
Fusarium Graminearum ◽  
Succinate Dehydrogenase Inhibitor
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