Diversity and Evolution of Sensor Histidine Kinases in Eukaryotes

Histidine kinases (HKs) are primary sensor proteins that act in cell signaling pathways generically referred to as "two component systems" (TCSs). TCSs are among the most widely distributed transduction systems used by both prokaryotic and eukaryotic organisms to detect and respond to a broad range of environmental cues. The structure and distribution of HK proteins are now well documented in prokaryotes but information is still fragmentary for eukaryotes. Here, we have taken advantage of recent genomic resources to explore the structural diversity and the phylogenetic distribution of HKs in the prominent eukaryotic supergroups. Searches of the genomes of 67 eukaryotic species spread evenly throughout the phylogenetic tree of life identified 748 predicted HK proteins. Independent phylogenetic analyses of predicted HK proteins were carried out for each of the major eukaryotic supergroups. This allowed most of the compiled sequences to be categorised into previously described HK groups. Beyond the phylogenetic analysis of eukaryotic HKs, this study revealed some interesting findings: (i) characterisation of some previously undescribed eukaryotic HK groups with predicted functions putatively related to physiological traits; (ii) discovery of HK groups that were previously believed to be restricted to a single kingdom in additional supergroups and (iii) indications that some evolutionary paths have led to the appearance, transfer, duplication, and loss of HK genes in some phylogenetic lineages. This study provides an unprecedented overview of the structure and distribution of HKs in the Eukaryota and represents a first step towards deciphering the evolution of TCS signaling in living organisms

Caractérisation de gènes impliqués dans la pathogénicité de Scedosporium apiospermum

Signaling pathways are cellular circuits that allow organisms to perceive environmental signals and develop an adapted response. More particularly, in microorganisms, these transduction pathways are of utter importance to adapt to host constraints. In this context, a better knowledge of these circuits in human pathogens could lead to identifying new targets for the development of antimicrobials. Therefore, such research is part of a comprehensive approach aiming at supporting the fight against infectious diseases. In this context, the first part of this work consisted of the in silico exploration of the structure and distribution of protein histidine kinases in eukaryotic organisms.These "sensor" proteins play a significant role in the adaptation and virulence of microorganisms and, due to their absence in mammals, they constitute interesting therapeutic targets. In a second part, we propose a functional study of two genes encoding elements involved in cell signaling pathways potentially implicated in the adaptation of the pathogenic fungus Scedosporium apiospermum to the bronchial microenvironment encountered in the context of cystic fibrosis. The first gene encodes a transcription factor belonging to the zinc finger domain family and the second a protein kinase of the TOR pathway. This work provides new knowledge on cell signaling pathways in microorganismsLes voies de signalisation sont des circuits cellulaires permettant aux organismes de percevoir des signaux environnementaux et de développer une réponse adaptée. Plus particulièrement chez les microorganismes, ces voies de transduction sont de première importance dans le but de s’adapter aux contraintes liées à l’hôte. Dans ce cadre, une meilleure connaissance de ces circuits chez les pathogènes humains pourrait amener à l’identification de nouvelles cibles pour le développement d’antimicrobiens. De telles recherches s’inscrivent donc dans une démarche globale visant à soutenir la lutte contre les maladies infectieuses. Dans ce contexte, la première partie de ce travail a consisté en l’exploration in silico de la structure et la distribution des protéines histidine kinases chez les organismes eucaryotes. Ces protéines ‘senseurs’ jouent en effet un rôle majeur dans l’adaptation et la virulence des microorganismes et, de par leur absence chez les mammifères, elles constituent aujourd’hui des cibles thérapeutiques intéressantes. Dans une seconde partie, nous proposons une étude fonctionnelle de deux gènes codant des éléments intervenant dans des voies de signalisation cellulaire potentiellement impliquées dans l’adaptation du champignon pathogène Scedosporium apiospermum au microenvironnement bronchique rencontré dans le contexte de la mucoviscidose. Le premier gène code un facteur de transcription de la famille des domaines à doigts de zinc et le second une proteine kinase de la voie TOR. A son échelle, ce travail fournit de nouvelles connaissances sur les voies de signalisation cellulaires chez les microorganisme

Characterization of genes involved in the pathogenicity of Scedosporium apiospermum

Les voies de signalisation sont des circuits cellulaires permettant aux organismes de percevoir des signaux environnementaux et de développer une réponse adaptée. Plus particulièrement chez les microorganismes, ces voies de transduction sont de première importance dans le but de s’adapter aux contraintes liées à l’hôte. Dans ce cadre, une meilleure connaissance de ces circuits chez les pathogènes humains pourrait amener à l’identification de nouvelles cibles pour le développement d’antimicrobiens. De telles recherches s’inscrivent donc dans une démarche globale visant à soutenir la lutte contre les maladies infectieuses. Dans ce contexte, la première partie de ce travail a consisté en l’exploration in silico de la structure et la distribution des protéines histidine kinases chez les organismes eucaryotes. Ces protéines ‘senseurs’ jouent en effet un rôle majeur dans l’adaptation et la virulence des microorganismes et, de par leur absence chez les mammifères, elles constituent aujourd’hui des cibles thérapeutiques intéressantes. Dans une seconde partie, nous proposons une étude fonctionnelle de deux gènes codant des éléments intervenant dans des voies de signalisation cellulaire potentiellement impliquées dans l’adaptation du champignon pathogène Scedosporium apiospermum au microenvironnement bronchique rencontré dans le contexte de la mucoviscidose. Le premier gène code un facteur de transcription de la famille des domaines à doigts de zinc et le second une proteine kinase de la voie TOR. A son échelle, ce travail fournit de nouvelles connaissances sur les voies de signalisation cellulaires chez les microorganismesSignaling pathways are cellular circuits that allow organisms to perceive environmental signals and develop an adapted response. More particularly, in microorganisms, these transduction pathways are of utter importance to adapt to host constraints. In this context, a better knowledge of these circuits in human pathogens could lead to identifying new targets for the development of antimicrobials. Therefore, such research is part of a comprehensive approach aiming at supporting the fight against infectious diseases. In this context, the first part of this work consisted of the in silico exploration of the structure and distribution of protein histidine kinases in eukaryotic organisms.These "sensor" proteins play a significant role in the adaptation and virulence of microorganisms and, due to their absence in mammals, they constitute interesting therapeutic targets. In a second part, we propose a functional study of two genes encoding elements involved in cell signaling pathways potentially implicated in the adaptation of the pathogenic fungus Scedosporium apiospermum to the bronchial microenvironment encountered in the context of cystic fibrosis. The first gene encodes a transcription factor belonging to the zinc finger domain family and the second a protein kinase of the TOR pathway. This work provides new knowledge on cell signaling pathways in microorganism

CHASEing Cytokinin Receptors in Plants, Bacteria, Fungi, and Beyond

International audienc

Cytokinin Sensing in Bacteria

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Advances in understanding and managing Scedosporium respiratory infections in patients with cystic fibrosis

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Megaviruses: an involvement in phytohormone receptor gene transfer in brown algae?

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Cytokinin and Ethylene Cell Signaling Pathways from Prokaryotes to Eukaryotes

International audienceCytokinins (CKs) and ethylene (ET) are among the most ancient organic chemicals on Earth. A wide range of organisms including plants, algae, fungi, amoebae, and bacteria use these substances as signaling molecules to regulate cellular processes. Because of their ancestral origin and ubiquitous occurrence, CKs and ET are also considered to be ideal molecules for inter-kingdom communication. Their signal transduction pathways were first historically deciphered in plants and are related to the two-component systems, using histidine kinases as primary sensors. Paradoxically, although CKs and ET serve as signaling molecules in different kingdoms, it has been supposed for a long time that the canonical CK and ET signaling pathways are restricted to terrestrial plants. These considerations have now been called into question following the identification over recent years of genes encoding CK and ET receptor homologs in many other lineages within the tree of life. These advances shed new light on the dissemination and evolution of these hormones as both intra-and inter-specific communication molecules in prokaryotic and eukaryotic organisms