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Genetics behind the variability in sensitivity to the demethylation inhibitor (DMI) fungicides myclobutanil and tebuconazole in Venturia inaequalis
DMI (Demethylation Inhibitor) fungicides are the family of fungicides most commonly used
for the post infection control of apple scab disease, which is produced by the fungus
Venturia inaequalis. One of the most widely used DMI fungicides in the UK and many other
countries is myclobutanil. Strains resistant to myclobutanil have been reported across the
world, prompting a need to find new products effective against the disease and to improve
the existing knowledge about the genetics behind the resistance and the evolution process.
Attempts to design a new microplate-based assay to test for fungicide resistance were
unsuccessful.
A total of 40 isolates coming from two sources (a baseline orchard which had never been
sprayed with fungicides and a collection of orchards with disease control problems thought
to be a result from cases of fungicide resistance) were tested for resistance to fungicides
myclobutanil and tebuconazole, a recently introduced DMI fungicide. Results confirm the
trend of increased resistance to myclobutanil observed in other countries. Cross-resistance
was discovered between the two chemicals, which lowers the prospects of tebuconazole to
be used as a substitute to myclobutanil.
Sequencing of the target CYP51A1 gene did not find any mutations linked to resistance in the
gene sequence. An analysis of the progeny of a RxS cross for sensitivity to tebuconazole
revealed quantitative control of the sensitivity, involving at least two genes, in the studied
cross and possibly epistatic effects, reflected by the asymmetric distribution of the sensitivity
in the progeny. Computer modelling of the evolution of the resistance helped identify some factors that can
influence the rate of evolution. Most of the factors tested had a small effect on the
evolution (epistasis and inclusion of overwintered conidia in the primary inoculum). The
biggest effects were for fungicide coverage and fungicides with a strong post-symptomatic
antisporulant activity
Expression and Function of GABA Receptors in Myelinating Cells
Myelin facilitates the fast transmission of nerve impulses and provides metabolic support to axons. Differentiation of oligodendrocyte progenitor cells (OPCs) and Schwann cell (SC) precursors is critical for myelination during development and myelin repair in demyelinating disorders. Myelination is tightly controlled by neuron-glia communication and requires the participation of a wide repertoire of signals, including neurotransmitters such as glutamate, ATP, adenosine, or gamma-aminobutyric acid (GABA). GABA is the main inhibitory neurotransmitter in the central nervous system (CNS) and it is also present in the peripheral nervous system (PNS). The composition and function of GABA receptors (GABARs) are well studied in neurons, while their nature and role in glial cells are still incipient. Recent studies demonstrate that GABA-mediated signaling mechanisms play relevant roles in OPC and SC precursor development and function, and stand out the implication of GABARs in oligodendrocyte (OL) and SC maturation and myelination. In this review, we highlight the evidence supporting the novel role of GABA with an emphasis on the molecular identity of the receptors expressed in these glial cells and the possible signaling pathways involved in their actions. GABAergic signaling in myelinating cells may have potential implications for developing novel reparative therapies in demyelinating diseases.This work was supported by CIBERNED (CB06/05/0076; CM) and by grants from the Ministry of Economy and Competitiveness, Government of Spain (SAF2016-75292-R and PID2019-109724RB-I00; CM), Basque Government (IT1203-19; CM), CONACYT-Mexico (No. 252121; RA), PAPIIT-UNAM-Mexico (IN203519; RA) and NIH (R21AG053740 and R21MH113177; AL). MS-R was hired thanks to the Gangoiti Foundation (Bilbao). LB-C and RO hold fellowships from Basque Government and CONACYT-Mexico, respectively
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Cross-resistance between myclobutanil and tebuconazole and the genetic basis of tebuconazole resistance in Venturia inaequalis
BACKGROUND: Myclobutanil is one of the most widely used demethylation inhibitor (DMI) fungicides for the management of apple scab, caused by Venturia inaequalis. Strains of V. inaequalis resistant to myclobutanil have been reported across the world. Tebuconazole, another DMI fungicide, has been proposed as an alternative to myclobutanil, and the extent of cross-resistance with myclobutanil therefore needs to be evaluated. The sensitivity to tebuconazole and myclobutanil of a total of 40 isolates was determined. Half the isolates came from an isolated orchard which had never been sprayed with fungicides and half from orchards sprayed regularly with myclobutanil, but still with disease control problems. The progeny of a tebuconazole resistant (R) 脳 sensitive (S) V. inaequalis cross were analysed in order to improve understanding of the genetic control of tebuconazole sensitivity.
RESULTS: There is cross-resistance between myclobutanil and tebuconazole (r=0.91; P < 0.001). Sensitivity to tebuconazole of the progeny of a R脳S cross varied quantitatively in a pattern which implied at least two gene loci differing between the parental strains. In addition, the asymmetric distribution of the sensitivity in the progeny implied possible epistatic effects.
CONCLUSION: Resistance to myclobutanil and tebuconazole is strongly correlated. At least two genes are involved in the control of tebuconazole resistance in V. inaequalis