Infection, anti-microbien, modélisation, évolution
Présentation
Rattaché à Paris Diderot, à l'INSERM ainsi qu'à l'université Paris 13, IAME est une unité multidisciplinaire (approche expérimentale, épidémiologie, modélisation statistique et mathématique) afin d’identifier les paramètres écologiques et évolutifs de l’adaptation des micro-organismes, en particulier ceux impliqués dans la virulence et la résistance aux antibiotiques. Le laboratoire dépend de deux départements de l'Alliance pour les sciences de la vie et de la santé (AVIESAN) : Maladies Infectieuses et Santé Publique. Situé sur le campus de Paris Diderot à la Faculté de médecine de l'Hôpital Bichat dans le nord de Paris, et relié à plusieurs hôpitaux universitaires à proximité, il offre une occasion unique de mélanger les scientifiques et cliniciens impliqués dans la recherche sur les maladies infectieuses. L'équipe consacrée à l'épidémiologie de la diversité écologique de Escherichia coli travaille sur le site Xavier Bichat (Université Paris 7) et aux laboratoires de Bactériologie des hôpitaux Avicenne et Jean Verdier.
Thèmes de recherche
Malgré un siècle d'efforts de prévention et de contrôle souvent fructueux, les maladies infectieuses restent un problème majeur de santé publique causant 13 millions de morts chaque année. De nouvelles maladies émergent, d'autres quasiment disparues ressurgissent, et l'on assiste au développement de la résistance aux agents antimicrobiens.
Deux types de causes expliquent ces données : les changements démographiques, comportementaux et technologiques des sociétés humaines associés aux modifications écologiques de la planète apparus durant le XXème siècle, et la capacité constante des microorganismes à évoluer et s'adapter. L'adaptation des populations repose sur la création de diversité génétique et l'action de la sélection naturelle. Parmi les mutants créés aléatoirement, la sélection naturelle ne retient que les individus les plus adaptés, soit les plus à même de survivre et de se reproduire dans leur environnement. Si de nombreux travaux ont très largement éclairci les aspects moléculaires de la virulence microbienne, peu d'études en revanche se sont appliquées à détailler les origines et conséquences évolutives de cette virulence.
Le but de notre recherche est de mieux détailler les paramètres écologiques et évolutifs qui permettent l'adaptation des microorganismes commensaux et pathogènes, et notamment ceux qui sont impliqués dans la transition d'un état à l'autre. Deux aspects sont essentiels pour comprendre l'évolution des microorganismes : l'adéquation entre leur génome et leur environnement d'une part et les contraintes agissant sur leur mode d'adaptation d'autre part.
Pour étudier ces deux aspects, nous avons choisi l'espèce Escherichia coli/Shigella, qui comprend des souches commensales du tube digestif mais aussi responsables de nombreuses pathologies intestinales et extra-intestinales, ainsi que les bactériophages phiX174 and phi6. A l'aide d'une approche mêlant (i) analyse de données génomiques (séquences de génomes complets, séquences de quelques gènes chez de nombreux isolats, présence/absence et expression de gènes) et (ii) analyse de nombreux phénotypes (croissance, activité métabolique, résistance aux stress divers dont les antimicrobiens, colonisation et virulence dans divers modèles animaux, circonstances cliniques d'isolement) sur des panels d'isolats naturels, nous souhaitons comprendre comment les génomes des microorganismes ont évolué et le lien avec l'émergence de la virulence.
Equipements
Structures L2, Automates incubateur/lecteur de DO
[hal-03896453] Compared Efficacy of Four Preoxygenation Methods for Intubation in the ICU
Date: 13 12 月 2022 - 14:05
Desc: [...]
[hal-01526918] Estimating the Time to Diagnosis and the Chance of Spontaneous Clearance during Acute Hepatitis C in HIV-Infected Individuals
Date: 23 5 月 2017 - 17:25
Desc: Background. Hepatitis C virus (HCV) infection is often asymptomatic, and the date of infection is almost impossible to determine. Furthermore, spontaneous clearance (SC) may occur, but little is known about its time of occurrence. Methods. Data on human immunodeficiency virus (HIV)-HCV coinfected individuals were used to inform a stochastic simulation model of HCV viral load kinetics, alanine aminotransferase (ALT), and HCV antibodies during acute hepatitis C. The dates of diagnosis and potential SC were estimated through a Bayesian approach. Hepatitis C virus diagnosis was assumed to be based on an elevated ALT level detected during a control visit for HIV-infected individuals, which occurred every 3 months (scenario A) or every 6 months (scenario B). Results. We found that HCV diagnosis occurred after a median of 115 days and 170 days of infection in scenarios A and B, respectively. Among spontaneous clearers, SC occurred after a median time of 184 days after infection. Seven percent (scenario B) to 10% (scenario A) of SCs appeared more than 6 months after diagnosis, and 3% (both scenarios) of SCs appeared more than 1 year after diagnosis. Conclusions. Acute hepatitis C diagnosis occurs late in HIV-HCV coinfected individuals. Screening for HCV in HIV-infected individuals should be performed frequently to reduce delays. Our findings about late occurrence of SC support " wait and see " strategies for treatment initiation from an individual basis. However, early treatment initiation may reduce HCV transmission.
[hal-02612650] Infective endocarditis related to unusual microorganisms: a prospective population-based study
Date: 8 7 月 2020 - 11:11
Desc: Background - Increased access to heart valves through early surgery and progress in molecular microbiology have reduced the proportion of infective endocarditis (IE) with no microbiological documentation and increased the proportion of IE associated with unusual microorganisms. Methods - We performed an ancillary study of a large prospective population-based survey on IE. Unusual-microorganism IE was defined as definite IE (Duke-Li criteria) due to microorganisms other than streptococci, staphylococci, or enterococci. Results - Of 471 cases of documented IE, 46 (9.8%) were due to unusal microorganisms; the following were involved in >1 case: (n = 4), (n = 4), (n = 3), (n = 3), and (n = 2). Cases were documented with blood cultures (n = 37, 80.4%), heart valve polymerase chain reaction (PCR; n = 5), heart valve culture (n = 2), PCR on vertebral biopsy (n = 1), or serology (n = 1). As compared with IE due to staphylococci, streptococci, or enterococci (n = 420), IE due to unusual microorganisms occurred more frequently in patients with previously known heart disease (69.0% vs 44.3%; = .002), prosthetic valve (40.5% vs 18.1%; = .0006), longer duration of fever (mean, 35.1 ± 46.8 days vs 12.5 ± 17.8; = .003), and who were more often nosocomial (38.1% vs 20.2%; = .02). Conclusions - In this population-based study, 9.8% of IE cases were due to unusual microorganisms, with a predominance of anaerobes, yeast, and gram-negative bacilli. As compared with IE related to staphylococci, streptococci, or enterococci, IE cases related to unusual microorganisms were associated with previously known heart disease, prosthetic valve, longer duration of fever, and nosocomial acquisition. Trial registration - ORCID 0000-0003-3617-5411.
[hal-02640842] Switch to rilpivirine/emtricitabine/tenofovir single-tablet regimen of human immunodeficiency virus-1 RNA-suppressed patients, Agence Nationale de Recherches sur le SIDA et les hepatites virales CO3 Aquitaine Cohort, 2012-2014
Date: 28 5 月 2020 - 16:27
Desc: Background. The purpose of this study was to assess the efficacy and tolerability of combined antiretroviral therapy (cART) in human immunodeficiency virus (HIV)-1 virologically suppressed patients who switched to rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) as a single-tablet regimen (STR). Methods. A retrospective multicenter cohort study was performed between September 2012 and February 2014 in Bordeaux University Hospital-affiliated clinics. Patients with a plasma HIV viral load (VL) lower than 50 copies/mL and switching to STR were evaluated at baseline, 3, 6, 9, and 12 months from switch time (M3, M6, M9, M12) for VL and other biological parameters. Change from baseline in CD4 cell counts was evaluated at M6 and M12. Virological failure (VF) was defined as 2 consecutive VL >50 copies/mL. Results. Three hundred four patients were included in the analysis. Single-tablet regimen switch was proposed to 116 patients with adverse events, mostly efavirenz (EFV)-based (n = 59), and to 224 patients for cART simplification. Thirty of 196 patients with available genotype resistance test results displayed virus with >= 1 drug resistance mutation on reverse-transcriptase gene. After 12 months of follow-up, 93.4% (95.5% confidence interval, 89.9-96.2) of patients remained virologically suppressed. There was no significant change in CD4 cell count. During the study period, 5 patients experienced VF, one of them harboring RPV resistance mutation. Clinical cART tolerability improved in 79 patients overall (29.9%) at M6, especially neurological symptoms related to EFV. Fasting serum lipid profiles improved, but a significant estimated glomerular function rate decrease (-11 mL/min/1.73 m(2); P < 10(-4)) was observed. Conclusions. Overall, virologic suppression was maintained in patients after switching to RPV/TDF/FTC. This STR strategy was associated with improved tolerability.
Autres contacts
Hôpital Robert Debré
48, boulevard Sérurier
75935 PARIS CEDEX 19