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Rescooped by cheral from Molecular basis of fungicide resistance
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Frontiers | Multidrug resistance in fungi: regulation of transporter-encoding gene expression | Membrane Physiology and Membrane Biophysics

Frontiers | Multidrug resistance in fungi: regulation of transporter-encoding gene expression | Membrane Physiology and Membrane Biophysics | cheral | Scoop.it
A critical risk to the continued success of antifungal chemotherapy is the acquisition of resistance; a risk exacerbated by the few classes of effective antifungal drugs. Predictably, as the use of these drugs increases in the clinic, more resistant organisms can be isolated from patients. A particularly problematic form of drug resistance that routinely emerges in the major fungal pathogens is known as multidrug resistance. Multidrug resistance refers to the simultaneous acquisition of tolerance to a range of drugs via a limited or even single genetic change. This review will focus on recent progress in understanding pathways of multidrug resistance in fungi including those of most medical relevance. Analyses of multidrug resistance in Saccharomyces cerevisiae have provided the most detailed outline of multidrug resistance in a eukaryotic microorganism. Multidrug resistant isolates of S. cerevisiae typically result from changes in the activity of a pair of related transcription factors that in turn elicit overproduction of several target genes. Chief among these is the ATP-binding cassette-encoding gene PDR5. Interestingly, in the medically important Candida species, very similar pathways are involved in acquisition of multidrug resistance. In both C. albicans and C. glabrata, changes in the activity of transcriptional activator proteins elicits overproduction of a protein closely related to S. cerevisiae Pdr5 called Cdr1. The major filamentous fungal pathogen, Aspergillus fumigatus, was previously thought to acquire resistance to azole compounds (the principal antifungal drug class) via alterations in the azole drug target-encoding gene cyp51A. More recent data indicate that pathways in addition to changes in the cyp51A gene are important determinants in A. fumigatus azole resistance. We will discuss findings that suggest azole resistance in A. fumigatus and Candida species may share more mechanistic similarities than previously thought.

Via Steve Marek, Melvin Bolton
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Rescooped by cheral from Molecular basis of fungicide resistance
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The Emergence of Resistance to Fungicides - Hobbelen et al. - PLoS One

The Emergence of Resistance to Fungicides - Hobbelen et al. - PLoS One | cheral | Scoop.it

Many studies exist about the selection phase of fungicide resistance evolution, where a resistant strain is present in a pathogen population and is differentially selected for by the application of fungicides. The emergence phase of the evolution of fungicide resistance - where the resistant strain is not present in the population and has to arise through mutation and subsequently invade the population - has not been studied to date. Here, we derive a model which describes the emergence of resistance in pathogen populations of crops. There are several important examples where a single mutation, affecting binding of a fungicide with the target protein, shifts the sensitivity phenotype of the resistant strain to such an extent that it cannot be controlled effectively (‘qualitative’ or ‘single-step’ resistance). The model was parameterized for this scenario for Mycosphaerella graminicola on winter wheat and used to evaluate the effect of fungicide dose rate on the time to emergence of resistance for a range of mutation probabilities, fitness costs of resistance and sensitivity levels of the resistant strain. We also evaluated the usefulness of mixing two fungicides of differing modes of action for delaying the emergence of resistance. The results suggest that it is unlikely that a resistant strain will already have emerged when a fungicide with a new mode of action is introduced. Hence, ‘anti-emergence’ strategies should be identified and implemented. For all simulated scenarios, the median emergence time of a resistant strain was affected little by changing the dose rate applied, within the range of doses typically used on commercial crops. Mixing a single-site acting fungicide with a multi-site acting fungicide delayed the emergence of resistance to the single-site component. Combining the findings with previous work on the selection phase will enable us to develop more efficient anti-resistance strategies.


Via Melvin Bolton
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Rescooped by cheral from Plant Pathogenomics
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PLoS Genetics: Genomic Analysis of the Necrotrophic Fungal Pathogens Sclerotinia sclerotiorum and Botrytis cinerea

PLoS Genetics: Genomic Analysis of the Necrotrophic Fungal Pathogens Sclerotinia sclerotiorum and Botrytis cinerea | cheral | Scoop.it

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared to <1% of B. cinerea. The arsenal of genes associated with necrotrophic processes is similar between the species, including genes involved in plant cell wall degradation and oxalic acid production. Analysis of secondary metabolism gene clusters revealed an expansion in number and diversity of B. cinerea–specific secondary metabolites relative to S. sclerotiorum. The potential diversity in secondary metabolism might be involved in adaptation to specific ecological niches. Comparative genome analysis revealed the basis of differing sexual mating compatibility systems between S. sclerotiorum and B. cinerea. The organization of the mating-type loci differs, and their structures provide evidence for the evolution of heterothallism from homothallism. These data shed light on the evolutionary and mechanistic bases of the genetically complex traits of necrotrophic pathogenicity and sexual mating. This resource should facilitate the functional studies designed to better understand what makes these fungi such successful and persistent pathogens of agronomic crops.


Via Kamoun Lab @ TSL
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Rescooped by cheral from Molecular basis of fungicide resistance
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Exploitation of genomics in fungicide research: current status and future perspectives - Cools - 2012 - Molecular Plant Pathology

Exploitation of genomics in fungicide research: current status and future perspectives - Cools - 2012 - Molecular Plant Pathology | cheral | Scoop.it

Every year, fungicide use to control plant disease caused by pathogenic fungi increases. The global fungicide market is now worth more than £5.3 billion, second only to the herbicide market in importance. In the UK, over 5500 tonnes of fungicide were applied to crops in 2010 (The Food and Environment Research Agency, Pesticide Usage Statistics), with 95.5% of the wheat-growing area receiving three fungicide sprays. Although dependence on fungicides to produce food securely, reliably and cheaply may be moderated in the future by further developments in crop biotechnology, modern crop protection will continue to require a diversity of solutions, including effective and safe chemical control. Therefore, investment in exploiting the increasingly available genome sequences of the most devastating fungal and oomycete phytopathogenic species should bring an array of new opportunities for chemical intervention. To date, the impact of whole genome research on the development, introduction and stewardship of fungicides has been limited, but ongoing improvements in computational analysis, molecular biology, chemical genetics, genome sequencing and transcriptomics will facilitate the development and registration of the future suite of crop protection chemicals.


Via Melvin Bolton
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Rescooped by cheral from Plant pathogens and pests
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The Transcription Factor BcLTF1 Regulates Virulence and Light Responses in the Necrotrophic Plant Pathogen Botrytis cinerea

The Transcription Factor BcLTF1 Regulates Virulence and Light Responses in the Necrotrophic Plant Pathogen Botrytis cinerea | cheral | Scoop.it

Botrytis cinerea is the causal agent of gray mold diseases in a range of dicotyledonous plant species. The fungus can reproduce asexually by forming macroconidia for dispersal and sclerotia for survival; the latter also participate in sexual reproduction by bearing the apothecia after fertilization by microconidia. Light induces the differentiation of conidia and apothecia, while sclerotia are exclusively formed in the absence of light. The relevance of light for virulence of the fungus is not obvious, but infections are observed under natural illumination as well as in constant darkness. By a random mutagenesis approach, we identified a novel virulence-related gene encoding a GATA transcription factor (BcLTF1 for light-responsive TF1) with characterized homologues in Aspergillus nidulans (NsdD) and Neurospora crassa (SUB-1). By deletion and over-expression of bcltf1, we confirmed the predicted role of the transcription factor in virulence, and discovered furthermore its functions in regulation of light-dependent differentiation, the equilibrium between production and scavenging of reactive oxygen species (ROS), and secondary metabolism. Microarray analyses revealed 293 light-responsive genes, and that the expression levels of the majority of these genes (66%) are modulated by BcLTF1. In addition, the deletion of bcltf1 affects the expression of 1,539 genes irrespective of the light conditions, including the overexpression of known and so far uncharacterized secondary metabolism-related genes. Increased expression of genes encoding alternative respiration enzymes, such as the alternative oxidase (AOX), suggest a mitochondrial dysfunction in the absence of bcltf1. The hypersensitivity of Δbctlf1 mutants to exogenously applied oxidative stress - even in the absence of light - and the restoration of virulence and growth rates in continuous light by antioxidants, indicate that BcLTF1 is required to cope with oxidative stress that is caused either by exposure to light or arising during host infection.

 

 


Via Christophe Jacquet
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