Different epidemiology of bloodstream infections in COVID-19 compared to non-COVID-19 critically ill patients: A descriptive analysis of the Eurobact II study

Background: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients. Methods: We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients’ characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models. Results: A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45). Conclusions: We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality. Trial registration ClinicalTrials.org number NCT03937245. Registered 3 May 2019

Aguas del Iténez o Guaporé

Bolivia y Brasil comparten una de las cuencas más atractivas y preservadas de la te-giuri amazônica: la cuenca del rio llénez o Guaporé, que escurre tanto sobre el lecho rocoso del Escudo Precámbrico Brasilefto como sobre las Hanuras del Beni. Estas influencias hacen que la cuenca del iténez tenga una elevada heterogeneidad de habitats, una fauna acuálica peculiar y un alto valor de conservation. Este patrimo­nio binacional posée un potencial importante para la conservación de la diversidad regional y cl dcsar rollo sostcniblc participativo de las comunidades locales. El libro contiene un resumen del conotimìento de la cuenca y sus recursos, generado en los últimos 10 anos por un equipo de investigadores bolivianos, brasilefios y de otras nacionalidades. Se presenta una descripeión del medio fisico, así como resultados relevantes sobre la biodiversidad acuática, con énfasis en algas, peces, reptiles y mamíferos. El aporte más notable del libro, adernas de la descripeión ecológica del ecosistema, son las lecciones aprendidas que surgieron de experiências locales sobre la élaboration participativa de herramientas para la gestion de los recursos hidrobiológicos.A Bolívia e o Brasil compartilham uma das bacias hidrográficas mais atrativas e preservadas da região amazônica: a bacia do Rio Iténez ou Guaporé. A combinação das influências do escudo pré-cambriano brasileiro e da planícies do Beni é uma das razões pela qual existem na região elevada heterogeneidade de habitats, fauna aquática peculiar e alto grau valor dc conservação. Eslc patrimônio binacional possui potencial significativo para a conservação da diversidade regional e desenvolvimento sustentável participativo das comunidades locais. O livro contém um resumo do conhecimento da bacia e seus recursos, gerado nos últimos dez anos por uma equipe de pesquisadores bolivianos, brasileiros e de outras nacionalidades. Apresentamos uma descrição do meio físico, bem como resultados relevantes da biodiversidade aquática, com ênfase em algas, peixes, répteis e mamíferos. A contribuição mais notável do livro, além da descrição ecológica do ecossistema, é a descrição das lições aprendidas que surgiram a partir de experiências locais sobre elaboração participativa de ferramentas para a gestão dos recursos aquáticos presentes nesta bacia

Régulation de la transcription des gènes de virulence bactériens : dynamique des complexes nucléoprotéïques

Bacteria face frequent environmental changes. Transcriptional regulation plays a major role in the adaptation to these changes. In particular, the phytopathogen bacteria Dickeya have recently adapted to vegetal hosts. They produce Pecate lyases (Pel), among others, to degrade pectin in plant cell walls, which is necessary for disease development. The pelD and pelE genes, despite the strong divergence in their expression, originate from a horizontal gene transfer followed by a recent duplication. This raises the question of their integration into the preexisting regulatory networks.Detailed molecular mechanisms of the transcriptional regulation of pelD were studied first. It was shown that this regulation relies on a high-affinity but low transcription efficiency divergent promoter and a strategic arrangement of four FIS repressor binding sites and two CRP activator binding sites. These elements interact together to fine-tune the expression of pelD. Next, the origin of the regulatory divergence between the paralogous genes pelD and pelE was explored. Surprisingly, their divergence and selection relies mostly on a TSS turnover which happened on the pelE regulatory region and transformed pelE into an initiator of pectin degradation. This widespread phenomenon in multicellular eukaryotes (human, fly, mouse…) had not yet been seen in bacteria. To conclude, through the study of D. dadantii pelD and pelE promoters, new mechanisms highlighting the relevance of transcriptional regulation in adaptation were discovered in this workLes bactéries sont en permanence confrontées à des changements d'environnements. La régulation transcriptionnelle joue alors un rôle majeur dans l'adaptation des bactéries. En particulier, la bactérie phytopathogène D. dadantii s'est récemment adaptée à l'hôte végétal. Elle produit en particulier des pectate lyases (Pel) qui dégradent la pectine, ciment des parois végétales, et jouent un rôle majeur dans le développement de la maladie. Les gènes pelD et pelE, malgré la forte divergence dans leur expression, sont issus d'un transfert horizontal suivi d'une duplication récente. La question de l'intégration de ces gènes avec les régulations préexistantes s'est alors posée.Dans un premier temps, les mécanismes moléculaires détaillés de la régulation de pelD ont été étudiés. Il a été montré que cette régulation s'appuie sur un promoteur divergent de forte affinité pour l'ARN polymérase mais de faible efficacité pour la transcription et sur un arrangement stratégique de quatre sites de fixation de répresseur FIS et deux sites de l'activateur CRP. Tous ces éléments interagissent entre eux pour produire une régulation fine de l'expression de pelD. L'origine de la divergence régulatrice entre les paralogues pelD et pelE a par la suite été explorée. De manière surprenante, la divergence entre ces deux gènes et leur sélection s'appuie presque exclusivement sur un décalage de la position du promoteur de pelE (« TSS turnover ») qui l'a transformé en initiateur de la dégradation de la pectine. Ce mécanisme très fréquent chez les eucaryotes pluricellulaires (homme, drosophile, souris…) n'avait jamais encore été décrit chez les bactéries.A travers l'étude des promoteurs pelD et pelE de D. dadantii, de nouveaux mécanismes renforçant l'importance de la régulation transcriptionnelle dans les processus adaptatifs ont ainsi été découvert

Dynamics of nucleoprotein complexes in the transcriptional regulation of bacterial virulence genes

Les bactéries sont en permanence confrontées à des changements d'environnements. La régulation transcriptionnelle joue alors un rôle majeur dans l'adaptation des bactéries. En particulier, la bactérie phytopathogène D. dadantii s'est récemment adaptée à l'hôte végétal. Elle produit en particulier des pectate lyases (Pel) qui dégradent la pectine, ciment des parois végétales, et jouent un rôle majeur dans le développement de la maladie. Les gènes pelD et pelE, malgré la forte divergence dans leur expression, sont issus d'un transfert horizontal suivi d'une duplication récente. La question de l'intégration de ces gènes avec les régulations préexistantes s'est alors posée.Dans un premier temps, les mécanismes moléculaires détaillés de la régulation de pelD ont été étudiés. Il a été montré que cette régulation s'appuie sur un promoteur divergent de forte affinité pour l'ARN polymérase mais de faible efficacité pour la transcription et sur un arrangement stratégique de quatre sites de fixation de répresseur FIS et deux sites de l'activateur CRP. Tous ces éléments interagissent entre eux pour produire une régulation fine de l'expression de pelD. L'origine de la divergence régulatrice entre les paralogues pelD et pelE a par la suite été explorée. De manière surprenante, la divergence entre ces deux gènes et leur sélection s'appuie presque exclusivement sur un décalage de la position du promoteur de pelE (« TSS turnover ») qui l'a transformé en initiateur de la dégradation de la pectine. Ce mécanisme très fréquent chez les eucaryotes pluricellulaires (homme, drosophile, souris…) n'avait jamais encore été décrit chez les bactéries.A travers l'étude des promoteurs pelD et pelE de D. dadantii, de nouveaux mécanismes renforçant l'importance de la régulation transcriptionnelle dans les processus adaptatifs ont ainsi été découvertsBacteria face frequent environmental changes. Transcriptional regulation plays a major role in the adaptation to these changes. In particular, the phytopathogen bacteria Dickeya have recently adapted to vegetal hosts. They produce Pecate lyases (Pel), among others, to degrade pectin in plant cell walls, which is necessary for disease development. The pelD and pelE genes, despite the strong divergence in their expression, originate from a horizontal gene transfer followed by a recent duplication. This raises the question of their integration into the preexisting regulatory networks.Detailed molecular mechanisms of the transcriptional regulation of pelD were studied first. It was shown that this regulation relies on a high-affinity but low transcription efficiency divergent promoter and a strategic arrangement of four FIS repressor binding sites and two CRP activator binding sites. These elements interact together to fine-tune the expression of pelD. Next, the origin of the regulatory divergence between the paralogous genes pelD and pelE was explored. Surprisingly, their divergence and selection relies mostly on a TSS turnover which happened on the pelE regulatory region and transformed pelE into an initiator of pectin degradation. This widespread phenomenon in multicellular eukaryotes (human, fly, mouse…) had not yet been seen in bacteria. To conclude, through the study of D. dadantii pelD and pelE promoters, new mechanisms highlighting the relevance of transcriptional regulation in adaptation were discovered in this wor

Régulation de la transcription des gènes de virulence bactériens : dynamique des complexes nucléoprotéïques

Bacteria face frequent environmental changes. Transcriptional regulation plays a major role in the adaptation to these changes. In particular, the phytopathogen bacteria Dickeya have recently adapted to vegetal hosts. They produce Pecate lyases (Pel), among others, to degrade pectin in plant cell walls, which is necessary for disease development. The pelD and pelE genes, despite the strong divergence in their expression, originate from a horizontal gene transfer followed by a recent duplication. This raises the question of their integration into the preexisting regulatory networks.Detailed molecular mechanisms of the transcriptional regulation of pelD were studied first. It was shown that this regulation relies on a high-affinity but low transcription efficiency divergent promoter and a strategic arrangement of four FIS repressor binding sites and two CRP activator binding sites. These elements interact together to fine-tune the expression of pelD. Next, the origin of the regulatory divergence between the paralogous genes pelD and pelE was explored. Surprisingly, their divergence and selection relies mostly on a TSS turnover which happened on the pelE regulatory region and transformed pelE into an initiator of pectin degradation. This widespread phenomenon in multicellular eukaryotes (human, fly, mouse…) had not yet been seen in bacteria. To conclude, through the study of D. dadantii pelD and pelE promoters, new mechanisms highlighting the relevance of transcriptional regulation in adaptation were discovered in this workLes bactéries sont en permanence confrontées à des changements d'environnements. La régulation transcriptionnelle joue alors un rôle majeur dans l'adaptation des bactéries. En particulier, la bactérie phytopathogène D. dadantii s'est récemment adaptée à l'hôte végétal. Elle produit en particulier des pectate lyases (Pel) qui dégradent la pectine, ciment des parois végétales, et jouent un rôle majeur dans le développement de la maladie. Les gènes pelD et pelE, malgré la forte divergence dans leur expression, sont issus d'un transfert horizontal suivi d'une duplication récente. La question de l'intégration de ces gènes avec les régulations préexistantes s'est alors posée.Dans un premier temps, les mécanismes moléculaires détaillés de la régulation de pelD ont été étudiés. Il a été montré que cette régulation s'appuie sur un promoteur divergent de forte affinité pour l'ARN polymérase mais de faible efficacité pour la transcription et sur un arrangement stratégique de quatre sites de fixation de répresseur FIS et deux sites de l'activateur CRP. Tous ces éléments interagissent entre eux pour produire une régulation fine de l'expression de pelD. L'origine de la divergence régulatrice entre les paralogues pelD et pelE a par la suite été explorée. De manière surprenante, la divergence entre ces deux gènes et leur sélection s'appuie presque exclusivement sur un décalage de la position du promoteur de pelE (« TSS turnover ») qui l'a transformé en initiateur de la dégradation de la pectine. Ce mécanisme très fréquent chez les eucaryotes pluricellulaires (homme, drosophile, souris…) n'avait jamais encore été décrit chez les bactéries.A travers l'étude des promoteurs pelD et pelE de D. dadantii, de nouveaux mécanismes renforçant l'importance de la régulation transcriptionnelle dans les processus adaptatifs ont ainsi été découvert

DNA supercoiling differences in bacteria result from disparate DNA gyrase activation by polyamines.

DNA supercoiling is essential for all living cells because it controls all processes involving DNA. In bacteria, global DNA supercoiling results from the opposing activities of topoisomerase I, which relaxes DNA, and DNA gyrase, which compacts DNA. These enzymes are widely conserved, sharing >91% amino acid identity between the closely related species Escherichia coli and Salmonella enterica serovar Typhimurium. Why, then, do E. coli and Salmonella exhibit different DNA supercoiling when experiencing the same conditions? We now report that this surprising difference reflects disparate activation of their DNA gyrases by the polyamine spermidine and its precursor putrescine. In vitro, Salmonella DNA gyrase activity was sensitive to changes in putrescine concentration within the physiological range, whereas activity of the E. coli enzyme was not. In vivo, putrescine activated the Salmonella DNA gyrase and spermidine the E. coli enzyme. High extracellular Mg2+ decreased DNA supercoiling exclusively in Salmonella by reducing the putrescine concentration. Our results establish the basis for the differences in global DNA supercoiling between E. coli and Salmonella, define a signal transduction pathway regulating DNA supercoiling, and identify potential targets for antibacterial agents

Transcriptional start site turnover in the evolution of bacterial paralogous genes - the pelE-pelD virulence genes in Dickeya

International audienc

Effect of various upper limb multibody models on soft tissue artefact correction: A case study

Soft tissue artefacts (STA) introduce errors in joint kinematics when using cutaneous markers, especially on the scapula. Both segmental optimisation and multibody kinematics optimisation (MKO) algorithms have been developed to improve kinematics estimates. MKO based on a chain model with joint constraints avoids apparent joint dislocation but is sensitive to the biofidelity of chosen joint constraints. Since no recommendation exists for the scapula, our objective was to determine the best models to accurately estimate its kinematics. One participant was equipped with skin markers and with an intracortical pin screwed in the scapula. Segmental optimisation and MKO for 24-chain models (including four variations of the scapulothoracic joint) were compared against the pin-derived kinematics using root mean square error (RMSE) on Cardan angles. Segmental optimisation led to an accurate scapula kinematics (1.1° ≤ RMSE ≤ 3.3°) even for high arm elevation angles. When MKO was applied, no clinically significant difference was found between the different scapulothoracic models (0.9° ≤ RMSE ≤ 4.1°) except when a free scapulothoracic joint was modelled (1.9° ≤ RMSE ≤ 9.6°). To conclude, using MKO as a STA correction method was not more accurate than segmental optimisation for estimating scapula kinematics

Transcriptional start site turnover in the evolution of bacterial paralogous genes - the pelE-pelD virulence genes in Dickeya

International audienc

Kinematic models of the upper limb joints for multibody kinematics optimisation: An overview

Soft tissue artefact (STA), i.e. the motion of the skin, fat and muscles gliding on the underlying bone, may lead to a marker position error reaching up to 8.7cm for the particular case of the scapula. Multibody kinematics optimisation (MKO) is one of the most efficient approaches used to reduce STA. It consists in minimising the distance between the positions of experimental markers on a subject skin and the simulated positions of the same markers embedded on a kinematic model. However, the efficiency of MKO directly relies on the chosen kinematic model. This paper proposes an overview of the different upper limb models available in the literature and a discussion about their applicability to MKO. The advantages of each joint model with respect to its biofidelity to functional anatomy are detailed both for the shoulder and the forearm areas. Models capabilities of personalisation and of adaptation to pathological cases are also discussed. Concerning model efficiency in terms of STA reduction in MKO algorithms, a lack of quantitative assessment in the literature is noted. In priority, future studies should concern the evaluation and quantification of STA reduction depending on upper limb joint constraints