Etude du zinc et des ATPases de type P dans l'interaction entre Mycobacterium tuberculosis et les cellules hôtes

Après infection d'une cellule hôte, telle qu'un macrophage, Mycobacterium tuberculosis (M. tuberculosis) réside à l'intérieur d'un phagosome et est soumis aux actions cellulaires visant à l'éliminer. Afin de survivre et se multiplier, le bacille a développé des stratégies pour combattre ou contourner ces mécanismes bactéricides. Une étude portant sur l'interaction entre M. tuberculosis et les cellules-hôtes, cellules dendritiques et macrophages, a révélé l'existence d'une famille de gènes mycobactériens fortement exprimés au cours de l'infection. Ces gènes codent pour des Ctp, protéines appartenant à la famille des ATPases de type PIB et prédites pour transporter des métaux de transition tels que Zn2+, Cd2+ ou Cu+. De façon complémentaire, la modulation de gènes cellulaires impliqués dans l'homéostasie du zinc a été mise en évidence. A partir de ces résultats, nous avons pu montrer qu'après infection par M. tuberculosis se produit une libération massive de zinc à l'intérieur du macrophage, et qu'une partie de ce zinc s'accumule dans le phagosome. En réaction cet afflux massif de zinc, le bacille active les systèmes d'export du métal, dont l'ATPase de type P CtpC. En effet, un mutant inactivé dans le gène codant pour CtpC et très sensible au zinc et est atténué dans sa capacité à parasiter les macrophages. L'ensemble de ces résultats a pu être reproduit avec une souche sauvage et un mutant inactivé dans le gène codant pour l'ATPase de type P ZntA responsable de l'efflux du zinc chez Escherichia coli, suggérant que l'utilisation du zinc par les cellules immunitaires pour empoisonner les microorganismes est un mécanisme général de l'immunité innée antimicrobienne.Mycobacterium tuberculosis thrives within macrophages by residing in phagosomes and preventing them from maturing and fusing with lysosomes. A parallel transcriptional survey of intracellular mycobacteria and their host macrophages revealed signatures of heavy metal poisoning, in particular, mycobacterial genes encoding P-type ATPases CtpC, CtpG, and CtpV. These proteins are predicted to export heavy metals, such as Zn2+, Cd2+ or Cu+. In the host cell transcriptome, genes coding for metallothioneins and the zinc exporter ZnT1, were induced during infection. Consistent with this pattern of gene modulation, we observed a burst of free zinc inside macrophages, and Intraphagosomal zinc accumulation within a few hours postinfection. Zinc exposure led to rapid CtpC induction, and ctpC deficiency caused zinc retention within the mycobacterial cytoplasm, leading to impaired intracellular growth of the bacilli. Using a deficient strain of Escherichia coli in zntA, coding for its main zinc exporter, we obtained the same results of zinc accumulation and impairment of the growth in macrophages. Thus, the use of P1-type ATPases represents a M. tuberculosis strategy to neutralize the toxic effects of zinc in macrophages. We propose that heavy metal toxicity and its counteraction might represent yet another chapter in the host-microbe arms race

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

Étude du zinc et des ATPases de type P dans l'interaction entre Mycobacterium tuberculosis et les cellules hôtes

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Experimental study, via current–potential curves, of the anodic behavior of Alloy C-276 and T60 titanium in chlorinated and oxygenated aqueous media under sub- to supercritical conditions

This paper presents the behavior of Alloy C-276 and T60 titanium, submitted to anodic polarization under steady-state and quasi-stationary conditions in oxidative chlorinated aqueous media. The measurements were carried out at temperatures and pressures from usual conditions (20 °C, 0.1 MPa) to supercritical conditions (400 °C, 28 MPa). The influence of various parameters such as pH, chloride ions activity, nature of materials, sub or supercritical state of the medium, was investigated. The effect of the temperature gave rise to the determination of activation energies of the dissolution–passivation processes. The hierarchy of the electrochemical behavior of the materials confirmed the results already obtained in a prevoius work using the determination of corrosion rates

Titanium dissolution-passivation in highly chloridic and oxygenated aqueous solutions

The principal objective of this paper is to show that we developed an experimental setup and a dissolution-passivation monitoring technique for use in super critical water oxidation (SCWO) conditions..

Electrochemical study of corrosion in aqueous high pressure, high temperature media and measurements of materials corrosion rates: applications to the hydrothermal treatments of organic wastes by SCWO

This paper presents, using a specific experimental set-up, the cathodic polarization curves recorded under steady-state and quasi-stationary conditions, for 316L stainless steel, Alloy C-276 and T60 titanium materials, in oxidative chlorinated aqueous media. Measurements were carried out at temperatures and pressures reaching supercritical conditions (400 °C, 28 MPa). The influence of various parameters such as the pH, the nature of materials, the sub- or supercritical state of the medium, was investigated using the determination of the corrosion rate. A hierarchy of the electrochemical behavior of the materials was established as far as the resistance to corrosion of industrial plants is concerned

Étude du comportement électrochimique des matériaux (316L, Hastelloy C,T60) soumis aux contraintes du traitement hydrothermal des déchets organiques jusqu'au domaine supercritique (adaptation de moyens expérimentaux pour le calcul des vitesses de corrosion et la modélisation de la dissolution passivation en milieu chloruré peu acide)

BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

Experimental set-up for electrochemical measurements in hydrothermal sub- and supercritical oxidation: polarization curves, determination of corrosion rates and evaluation of the degradability of reactors during hydrothermal treatments of aqueous wastes

Electrochemical data concerning metallic materials submitted to aqueous media at high pressures and high temperatures, which are close to the critical point, are scarce. This is essentially due to the difficulties encountered during the setting-up of an appropriate system of analysis. This paper, in the peculiar context of organic wastes supercritical water oxidation, proposes, for both sub and supercritical conditions, some technical solutions to define a cell able to give access to quantitative electrochemical information. For special media (pH≥1.7 and chloride ions content≈1 g/l), using a specific device consisted of a TA6V electrochemical cell, ensuring lasting and chemically inert electrical isolation and water tightness, along with a hydrogen dynamic electrode (HDE), it is possible to obtain reliable ‘current–potential' curves allowing a quantitative exploitation, particularly for corrosion rates determination

Metallobiology of host–pathogen interactions: an intoxicating new insight

International audienc