CcpA represses the expression of the divergent cit operons of Enterococcus faecalis through multiple cre sites

<p>Abstract</p> <p>Background</p> <p>In <it>Enterococcus faecalis </it>the genes encoding the enzymes involved in citrate metabolism are organized in two divergent operons, <it>citHO </it>and <it>oadHDB-citCDEFX-oadA-citMG </it>(<it>citCL </it>locus). Expression of both operons is specifically activated by adding citrate to the medium. This activation is mediated by binding of the GntR-like transcriptional regulator (CitO) to the <it>cis</it>-acting sequences located in the <it>cit </it>intergenic region. Early studies indicated that citrate and glucose could not be co-metabolized suggesting some form of catabolite repression, however the molecular mechanism remained unknown.</p> <p>Results</p> <p>In this study, we observed that the <it>citHO </it>promoter is repressed in the presence of sugars transported by the Phosphoenolpyruvate:carbohydrate Phosphotranserase System (PTS sugars). This result strongly suggested that Carbon Catabolic Repression (CCR) impedes the expression of the activator CitO and the subsequent induction of the <it>cit </it>pathway. In fact, we demonstrate that CCR is acting on both promoters. It is partially relieved in a <it>ccpA</it>-deficient <it>E. faecalis </it>strain indicating that a CcpA-independent mechanism is also involved in regulation of the two operons. Furthermore, sequence analysis of the <it>citH</it>/<it>oadH </it>intergenic region revealed the presence of three putative catabolite responsive elements (<it>cre</it>). We found that they are all active and able to bind the CcpA/P-Ser-HPr complex, which downregulates the expression of the <it>cit </it>operons. Systematic mutation of the CcpA/P-Ser-HPr binding sites revealed that <it>cre1 </it>and <it>cre2 </it>contribute to <it>citHO </it>repression, while <it>cre3 </it>is involved in CCR of <it>citCL</it></p> <p>Conclusion</p> <p>In conclusion, our study establishes that expression of the <it>cit </it>operons in <it>E. faecalis </it>is controlled by CCR via CcpA-dependent and -independent mechanisms.</p

Role of Protein Phosphorylation in the Regulation of Cell Cycle and DNA-Related Processes in Bacteria

In all living organisms, the phosphorylation of proteins modulates various aspects of their functionalities. In eukaryotes, protein phosphorylation plays a key role in cell signaling, gene expression, and differentiation. Protein phosphorylation is also involved in the global control of DNA replication during the cell cycle, as well as in the mechanisms that cope with stress-induced replication blocks. Similar to eukaryotes, bacteria use Hanks-type kinases and phosphatases for signal transduction, and protein phosphorylation is involved in numerous cellular processes. However, it remains unclear whether protein phosphorylation in bacteria can also regulate the activity of proteins involved in DNA-mediated processes such as DNA replication or repair. Accumulating evidence supported by functional and biochemical studies suggests that phospho-regulatory mechanisms also take place during the bacterial cell cycle. Recent phosphoproteomics and interactomics studies identified numerous phosphoproteins involved in various aspect of DNA metabolism strongly supporting the existence of such level of regulation in bacteria. Similar to eukaryotes, bacterial scaffolding-like proteins emerged as platforms for kinase activation and signaling. This review reports the current knowledge on the phosphorylation of proteins involved in the maintenance of genome integrity and the regulation of cell cycle in bacteria that reveals surprising similarities to eukaryotes

Functional Characterization of the Incomplete Phosphotransferase System (PTS) of the Intracellular Pathogen Brucella melitensis

Background: In many bacteria, the phosphotransferase system (PTS) is a key player in the regulation of the assimilation of alternative carbon sources notably through catabolic repression. The intracellular pathogens Brucella spp. possess four PTS proteins (EI Ntr, NPr, EIIA Ntr and an EIIA of the mannose family) but no PTS permease suggesting that this PTS might serve only regulatory functions

Des formes de capitalisme à la dynamique de l'innovation: la question de la gestion des risques

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Variété de capitalisme et financement de l'innovation: Une comparaison Europe / Etats-Unis dans le cas des petites entreprises innovantes

Actes à paraîtreInternational audienceLa dynamique de l'innovation est liée aux financements mobilisés pour accompagner le développement des petites entreprises innovantes mais elle dépend également des caractéristiques institutionnelles d'une économie. Les différents types de capitalisme, proposés par les économistes de la régulation, en fournissent un cadre. En mettant en évidence la relation entre le type dominant de capitalisme et les modalités de gestion retenues pour le financement de ces entreprises innovantes, cette communication vise à apporter un éclairage particulier sur les différences observées entre les États-Unis et de nombreux pays européens. Ces différences reposent sur l'appréciation et la gestion des risques au sein des types de capitalisme. Lorsque la régulation financière s'opère à travers les marchés (market-based), comme aux Etats-Unis, la concordance entre le contexte institutionnel et le capital-risque explique certainement le succès du financement des petites entreprises innovantes. En effet, le risque financier n'y est pas supporté par un opérateur mais est, au contraire, dilué sur un grand nombre d'agents intervenant sur différents marchés avec des outils financiers appropriés. En revanche, dans un environnement où les pouvoirs publics jouent un rôle majeur dans la régulation économique (nombreux pays d'Europe continentale), où les banques occupent une place prépondérante dans la régulation financière (bank-based) quels résultats peuvent produire les opérations en capital-risque ? Dans le modèle bank-based, les réseaux traditionnels du financement de l'économie sont-ils compatibles avec la gestion des investissements en capital-risque ? L'efficacité comparée des deux modèles montre que si le financement privé de l'innovation privilégie le capital-risque, la logique de construction et d'implication des fonds se trouve fortement ancrée dans l'environnement qui les a générés. La transplantation des formes de financement par le capital-risque dans un contexte bank-based conduit à des résultats quelque peu ambigus. Le territoire apparaît alors comme l'une des clés de la dynamique institutionnelle supportant le processus d'innovation. 1 Sandrine.Michel@uni

Le processus d'hybridation des politiques territoriales, une lecture institutionnelle

International audienceLa communication explore la dynamique de transfert de politiques publiques territoriales en précisant d’un point de vue théorique les mécanismes en jeu et en donnant une illustration à partir de cas empiriques. On se place dans le cas où les politiques publiques cherchent à agir sur un territoire par transpositions mimétiques d’expériences qui ont produit des résultats concluants ailleurs. Si la définition des politiques publiques (objectifs, instruments) sont susceptibles de présenter un degré d’homogénéité élevé, en revanche les points d’application que sont les territoires présentent, quant à eux, une diversité agissante expliquant le processus d’hybridation institutionnelle et, au final, le succès ou l’échec des politiques. Le territoire est conçu ici comme un construit social agrégeant dans son fonctionnement une série d’institutions. Ces dernières entrent en relation avec les politiques publiques se présentant elles-mêmes comme des construits institutionnels

Le processus d’hybridation des politiques territoriales : une approche institutionnelle

Dans la définition d’une politique publique, les objectifs, le contenu, les résultats attendus sont privilégiés. Mais, lors de leur mise en œuvre, en dépit des cadrages méthodologiques et des diagnostics territoriaux initiaux, les territoires récepteurs se révèlent de puissants vecteurs de différenciation. En cela, l’analyse de la territorialisation de ces politiques ne peut se contenter d’une vision « administrative » ou réceptrice du territoire. Le territoire construit doit lui être substit..

Public Policy and Institutional Inertia: from the Hybirdization Process in the Territories Building

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Le processus d’hybridation des politiques territoriales : une approche institutionnelle

International audienc

Understanding sociotechnical organizational leeway and acting to increase it to prevent MSDs among care assistants in care homes for the elderly

International audienceMusculoskeletal disorders (MSDs) are the leading occupational disease in France, Europe, and internationally. Due to challenging working conditions, care assistants in care homes for the elderly are particularly affected. Care professions are increasingly less attractive, while needs are growing due to the societal context of ageing population. Restoring leeway to healthcare professionals is a challenge to support their caregiving activities and prevent MSDs. We distinguish two types of leeway: Situational Operational Leeway (SOL) which is the workers' ability to implement an efficient operating mode in a working situation, and SocioTechnical Organizational Leeway (STOL) which is the possibilities the work environment offers to workers. This research aims to understand STOL, its link with regulations and SOL, and ways to support the creation of new opportunities, to sustainably prevent MSDs. To understand the perceived and actual STOL, we implemented a mixed quantitative and qualitative approach. The quantitative approach is based on data from a questionnaire aimed to identify and assess perceived STOL. The qualitative approach is based on work analysis aimed to identify the use of the available STOL during care activities. In an attempt to help increasing STOL, we carried out a participatory approach through collective confrontations and presentations. The quantitative approach partly predicts actual STOL and provided a valuable tool for conveying the reality to decision-makers and guiding the intervention. The qualitative analysis supplements the quantitative analysis. It reveals new dimension of STOL, in particular the STOL offered by the resident. It shows links between STOL and the possibilities for regulation, revealing potential levers for action. STOL offered by colleagues and by participatory setting are particularly important to regulate when faced to resident care difficulties. The care assistants' and management's analysis of real work situations allowed them to create new STOL with varying effects on the actors' activity. It seems that the link between STOL and development of SOL depends particularly on the existing work collective. STOL diagnosis could be a useful tool for guiding the intervention towards building the one that is favourable to regulations and development of SOL to prevent MSDs among care assistants. Keywords Leeway, Musculoskeletal disorders, care assistants, care homes for the elderly Context Despite efforts to prevent the risks in past years, musculoskeletal disorders (MSDs) are still the leading occupational disease in France, Europe, and internationally. The residential care homes for the elderly sector is particularly affected. In 2019 in France, 94% of recognised occupational diseases were linked to MSDs 1