Fungicide sensitivity of Mycosphaerella graminicola Tunisian isolates: the importance of drug transporter genes in the process of fungicide tolerance

Seventeen Mycosphaerella graminicola isolates from Tunisia and two reference isolates from Europe (St-Q7-2 and IPO323) were examined for sensitivity to azoxystrobin and tebuconazole and for the importance of the drug transporter genes MgAtr3 (ABC transporter), MgMfs1 (MFS transporter), MgSlt2 (MAP Kinase), MgGpa1 and MgGpb1 (cyclic AMP) in the process of fungicide tolerance. All Tunisian isolates were sensitive to both fungicides, but considerable variability in sensitivity, and evidence for slight multidrug resistance toward both fungicides (r = 0.58), were observed. A gene expression assay revealed that MgAtr3 and MgMfs1 are involved in tolerance to both fungicides. MgAtr3 is likely involved in tolerance to tebuconazole, while MgMfs1 is likely required for tolerance to azoxystrobin. The other genes examined were found more likely to be pathogenicity factors rather than fungicide tolerance factors, except for MgSlt2 which was weakly induced by azoxystrobin treatment. This study has indicated that the Tunisian population of M. graminicola remains more sensitive to strobilurin and azole fungicides than European populations, and reports the importance of the ABC and MFS transporters MgAtr3 and MgMfs1 in the mechanism of fungicide tolerance

Implementation of the One Health approach to fight arbovirus infections in the Mediterranean and Black Sea Region: Assessing integrated surveillance in Serbia, Tunisia and Georgia

Background In the Mediterranean and Black Sea Region, arbovirus infections are emerging infectious diseases. Their surveillance can benefit from one health inter-sectoral collaboration; however, no standardized methodology exists to study One Health surveillance. Methods We designed a situation analysis study to document how integration of laboratory/clinical human, animal and entomological surveillance of arboviruses was being implemented in the Region. We applied a framework designed to assess three levels of integration: policy/institutional, data collection/data analysis and dissemination. We tested the use of Business Process Modelling Notation (BPMN) to graphically present evidence of inter-sectoral integration. Results Serbia, Tunisia and Georgia participated in the study. West Nile Virus surveillance was analysed in Serbia and Tunisia, Crimea-Congo Haemorrhagic Fever surveillance in Georgia. Our framework enabled a standardized analysis of One Health surveillance integration, and BPMN was easily understandable and conducive to detailed discussions among different actors/institutions. In all countries, we observed integration across sectors and levels except in data collection and data analysis. Data collection was interoperable only in Georgia without integrated analysis. In all countries, surveillance was mainly oriented towards outbreak response, triggered by an index human case. Discussion The three surveillance systems we observed prove that integrated surveillance can be operationalized with a diverse spectrum of options. However, in all countries, the integrated use of data for early warning and inter-sectoral priority setting is pioneeristic. We also noted that early warning before human case occurrence is recurrently not operationally prioritized

Similar infection process and induced defense patterns during compatible interactions between Zymoseptoria tritici and both bread and durum wheat species

International audienc

Oligogenic Inheritance Underlying Incomplete Penetrance of PROKR2 Mutations in Hypogonadotropic Hypogonadism

International audienceThe role of the prokineticin 2 pathway in human reproduction, olfactory bulb morphogenesis, and gonadotropin-releasing hormone secretion is well established. Recent studies have highlighted the implication of di/oligogenic inheritance in this disorder. In the present study, we aimed to identify the genetic mechanisms that could explain incomplete penetrance in hypogonadotropic hypogonadism (HH). This study involved two unrelated Tunisian patients with HH, which was triggered by identifying a homozygous p.(Pro290Ser) mutation in the PROKR2 gene in a girl (HH1) with Kallmann syndrome (KS). The functional effect of this variant has previously been well demonstrated. Unexpectedly, her unaffected father (HH1P) and brother (HH1F) also carried this genetic variation at a homozygous state. In the second family, we identified a heterozygous p.(Lys205del) mutation in PROKR2 , both in a male patient with normosmic idiopathic IHH (HH12) and his asymptomatic mother. Whole-exome sequencing in the three HH1 family members allowed the identification of additional variants in the prioritized genes. We then carried out digenic combination predictions using the oligogenic resource for variant analysis (ORVAL) software. For HH1, we found the highest number of disease-causing variant pairs. Notably, a CCDC141 variant (c.2803C > T) was involved in 18 pathogenic digenic combinations. The CCDC141 variant acts in an autosomal recessive inheritance mode, based on the digenic effect prediction data. For the second patient (HH12), prediction by ORVAL allowed the identification of an interesting pathogenic digenic combination between DUSP6 and SEMA7A genes, predicted as “dual molecular diagnosis.” The SEMA7A variant p.(Glu436Lys) is novel and predicted as a VUS by Varsome. Sanger validation revealed the absence of this variant in the healthy mother. We hypothesize that disease expression in HH12 could be induced by the digenic transmission of the SEMA7A and DUSP6 variants or a monogenic inheritance involving only the SEMA7A VUS if further functional assays allow its reclassification into pathogenic. Our findings confirm that homozygous loss-of-function genetic variations are insufficient to cause KS, and that oligogenism is most likely the main transmission mode involved in Congenital Hypogonadotropic Hypogonadism