Corrigendum: Investigating genetic diversity within the most abundant and prevalent non-pathogenic leaf-associated bacteria interacting with Arabidopsis thaliana in natural habitats

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Conception, synthèse et évaluation pharmacologique de nouveaux azolés à activité antifongique

Les infections fongiques invasives constituent une menace croissante pour la santé humaine. Ces infections se produisent principalement dans le contexte des thérapies immunosuppressives de plus en plus agressives. Malgré l'avènement de nouvelles stratégies de diagnostic et de traitements, la mortalité globale pour les maladies invasives causées par des espèces de Candida et d Aspergillus est de 30-50 %. La recherche de nouveaux agents antifongiques est principalement axée sur l'amélioration du spectre antifongique, le contournement de la résistance, la réduction de la toxicité et l'amélioration de la biodisponibilité. Parmi les traitements existants, les azolés agissent sur la biosynthèse de l'ergostérol (composant essentiel de la membrane plasmique) en inhibant la 14alpha-déméthylase, une enzyme à cytochrome P450 (CYP51), codée par le gène ERG11. Les recherches effectuées précédemment au laboratoire sur des inhibiteurs possédant le motif l-hétéroaryl-2-phényl-3-(lH- l,2,4-triazol-l-yl)propan-2-ol ont permis d'isoler des composés avec de fortes activités sur Candida albicans et avec une émergence d'activité sur Aspergillus fumigatus. Dans le prolongement de ces travaux, et afin de préciser les relations structure-activité, de nouveaux composés azolés (de structure indolique, benzènesulfonamide ou biaryle) ont été synthétisés et évalués. En parallèle, nous nous sommes intéressés à la synthèse d'analogues de l'albaconazole actuellement en phase III d'essais cliniques, par introduction de thiazoloquinazolinones via la chimie du sel d'Appel.Invasive fungal infections are an increasing threat to human health. These infections predominantly occur in the context of increasingly aggressive immunosuppressive therapies. The overall mortality for invasive diseases caused by Candida spp. and Aspergillus spp. is about 30-50, despite the advent of new diagnostic and therapeutic strategies. The search on new antifungal agents is mainly focused on the improvement of the antifungal spectrum, counteraction of resistance, reduction of toxicity and enhancement of bioavailability. Among the treatments, azoles act on the biosynthesis ofergosterol (major component of fungal membrane) by inhibiting P450-dependent lanosterol 14alpha-demethylase (CYP51),encoded by theeRG 11 gene. Previous researches in our laboratory have focused on inhibitors with 1-heteroaryl-2-phenyl-l-(17H-l,2,4-triazol-l-yl)propan-2-ol moiety. Those studies have resulted in isolation of compounds with potent activities against Candida albicans and an emergence of activity on Aspergillus fumigatus. On the basis of this study new azoles compounds (with indole, benzenesulfonamide or biaryle structure) were synthesized andevaluated in order to specify structure- activity relationships. In parallel, we synthesized analogues of albaconazole which is currently in phase III clinical trials, by introducing thiazoloquinazolinones via the Appel's salt chemistry.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

A genomic map of local adaptation in Arabidopsis thaliana to native non-pathogenic bacteria: from mono-infections to complex communities

National audienceThere is growing interest in the potential of harnessing the microbiome towards the improvement of plant health to achieve agricultural goals. To do so through plant breeding, requires a better understanding of the role of the host genome in modulating microbiota variation. In particular, there is a need to overcome the current limits on the description of host-microbiota interactions at the genomic and molecular levels. However, the host genetic architecture structuring microbiota is only partly described in plants. To dissect the genetic architecture driving adaptive plant-microbiota interactions, I will present the results of complementary approaches in association genetics applied on Arabidopsis thaliana: (i) a Genome-Environment Association (GEA) analysis on 141 whole-genome sequenced natural populations of A. thaliana characterized in situ for their leaf and root bacterial communities and a large set of non-microbial ecological factors (i.e., climate, soil, and plant communities), and (ii) a Genome-Wide Association study conducted in field conditions on 162 whole-genome sequenced accessions of A. thaliana inoculated with 13 native Plant Growth-Promoting Bacteria (PGPB) isolated from these populations. By combining these two approaches, we established a genomic map of local adaptation in A. thaliana to its native bacterial microbiota. Plant immunity appears as a major source of adaptive genetic variation structuring beneficial interactions between A. thaliana and the main members of its microbiota

A genomic map of local adaptation in Arabidopsis thaliana to native non-pathogenic bacteria: from mono-infections to complex communities

National audienceThere is growing interest in the potential of harnessing the microbiome towards the improvement of plant health to achieve agricultural goals. To do so through plant breeding, requires a better understanding of the role of the host genome in modulating microbiota variation. In particular, there is a need to overcome the current limits on the description of host-microbiota interactions at the genomic and molecular levels. However, the host genetic architecture structuring microbiota is only partly described in plants. To dissect the genetic architecture driving adaptive plant-microbiota interactions, I will present the results of complementary approaches in association genetics applied on Arabidopsis thaliana: (i) a Genome-Environment Association (GEA) analysis on 141 whole-genome sequenced natural populations of A. thaliana characterized in situ for their leaf and root bacterial communities and a large set of non-microbial ecological factors (i.e., climate, soil, and plant communities), and (ii) a Genome-Wide Association study conducted in field conditions on 162 whole-genome sequenced accessions of A. thaliana inoculated with 13 native Plant Growth-Promoting Bacteria (PGPB) isolated from these populations. By combining these two approaches, we established a genomic map of local adaptation in A. thaliana to its native bacterial microbiota. Plant immunity appears as a major source of adaptive genetic variation structuring beneficial interactions between A. thaliana and the main members of its microbiota

The genetic architecture of Arabidopsis thaliana in response to native non-pathogenic leaf bacterial species revealed by GWA mapping in field conditions

ABSTRACT Non-pathogenic bacteria can largely contribute to plant health by mobilizing and supplying nutrients and by providing protection against pathogens and resistance to abiotic stresses. Yet, the number of GWAS reporting the genetic architecture of the response to individual members of the beneficial microbiota remains limited. In this study, we established a GWAS under field conditions to estimate the level of genetic variation and the underlying genetic architecture, among 162 accessions of Arabidopsis thaliana originating from 54 natural populations located south-west of France, in response to 13 strains of seven of the most abundant and prevalent non-pathogenic bacterial species isolated from the leaf compartment of A. thaliana in the same geographical region. Using a high-throughput phenotyping methodology to score vegetative growth-related traits, extensive genetic variation was detected within our local set of A. thaliana accessions in response to these leaf bacteria, both at the species and strain levels. The presence of crossing reaction norms among strains indicates that declaring a strain as a plant-growth promoting bacterium is highly dependent on the host genotype tested. In line with the strong genotype-by-genotype interactions, we detected a complex and highly flexible genetic architecture between the 13 strains. Finally, the candidate genes underlying the QTLs revealed a significant enrichment in several biological pathways, including cell, secondary metabolism, signalling and transport. Altogether, plant innate immunity appears as a significant source of natural genetic variation in plant-microbiota interactions and opens new avenues for better understanding the ecologically relevant molecular dialog during plant-microbiota interactions

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Investigating genetic diversity within the most abundant and prevalent non-pathogenic leaf-associated bacteria interacting with Arabidopsis thaliana in natural habitats

International audienceMicrobiota modulates plant health and appears as a promising lever to develop innovative, sustainable and eco-friendly agro-ecosystems. Key patterns of microbiota assemblages in plants have been revealed by an extensive number of studies based on taxonomic profiling by metabarcoding. However, understanding the functionality of microbiota is still in its infancy and relies on reductionist approaches primarily based on the establishment of representative microbial collections. In Arabidopsis thaliana , most of these microbial collections include one strain per OTU isolated from a limited number of habitats, thereby neglecting the ecological potential of genetic diversity within microbial species. With this study, we aimed at estimating the extent of genetic variation between strains within the most abundant and prevalent leaf-associated non-pathogenic bacterial species in A. thaliana located south-west of France. By combining a culture-based collection approach consisting of the isolation of more than 7,000 bacterial colonies with an informative-driven approach, we isolated 35 pure strains from eight non-pathogenic bacterial species. We detected significant intra-specific genetic variation at the genomic level and for growth rate in synthetic media. In addition, significant host genetic variation was detected in response to most bacterial strains in in vitro conditions, albeit dependent on the developmental stage at which plants were inoculated, with the presence of both negative and positive responses on plant growth. Our study provides new genetic and genomic resources for a better understanding of the plant-microbe ecological interactions at the microbiota level. We also highlight the need of considering genetic variation in both non-pathogenic bacterial species and A. thaliana to decipher the genetic and molecular mechanisms involved in the ecologically relevant dialog between hosts and leaf microbiota

Design, Synthesis, and in vitro Antifungal Activity of 1-[(4-Substituted-benzyl)methylamino]-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ols

International audienc

Data_Sheet_1_Investigating genetic diversity within the most abundant and prevalent non-pathogenic leaf-associated bacteria interacting with Arabidopsis thaliana in natural habitats.zip

Microbiota modulates plant health and appears as a promising lever to develop innovative, sustainable and eco-friendly agro-ecosystems. Key patterns of microbiota assemblages in plants have been revealed by an extensive number of studies based on taxonomic profiling by metabarcoding. However, understanding the functionality of microbiota is still in its infancy and relies on reductionist approaches primarily based on the establishment of representative microbial collections. In Arabidopsis thaliana, most of these microbial collections include one strain per OTU isolated from a limited number of habitats, thereby neglecting the ecological potential of genetic diversity within microbial species. With this study, we aimed at estimating the extent of genetic variation between strains within the most abundant and prevalent leaf-associated non-pathogenic bacterial species in A. thaliana located south-west of France. By combining a culture-based collection approach consisting of the isolation of more than 7,000 bacterial colonies with an informative-driven approach, we isolated 35 pure strains from eight non-pathogenic bacterial species. We detected significant intra-specific genetic variation at the genomic level and for growth rate in synthetic media. In addition, significant host genetic variation was detected in response to most bacterial strains in in vitro conditions, albeit dependent on the developmental stage at which plants were inoculated, with the presence of both negative and positive responses on plant growth. Our study provides new genetic and genomic resources for a better understanding of the plant-microbe ecological interactions at the microbiota level. We also highlight the need of considering genetic variation in both non-pathogenic bacterial species and A. thaliana to decipher the genetic and molecular mechanisms involved in the ecologically relevant dialog between hosts and leaf microbiota.</p