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-01528905] Characteristics of and risk factors for severe neurological deficit in patients with pyogenic vertebral osteomyelitis: A case-control study.
Date: 2 7 月 2018 - 12:26
Desc: Severe neurological deficit (SND) is a rare but major complication of pyogenic vertebral osteomyelitis (PVO). We aimed to determine the risk factors and the variables associated with clinical improvement for SND during PVO.This case-control study included patients without PVO-associated SND enrolled in a prospective randomized antibiotic duration study, and patients with PVO-associated SND managed in 8 French referral centers. Risk factors for SND were determined by logistic regression.Ninety-seven patients with PVO-associated SND cases, and 297 controls were included. Risk factors for SND were epidural abscess [adjusted odds ratio, aOR 8.9 (3.8-21)], cervical [aOR 8.2 (2.8-24)], and/or thoracic involvement [aOR 14.8 (5.6-39)], Staphylococcus aureus PVO [aOR 2.5 (1.1-5.3)], and C-reactive protein (CRP) >150 mg/L [aOR 4.1 (1.9-9)]. Among the 81 patients with PVO-associated SND who were evaluated at 3 months, 62% had a favorable outcome, defined as a modified Rankin score ≤ 3. No factor was found significantly associated with good outcome, whereas high Charlson index [adjusted Hazard Ratio (aHR) 0.3 (0.1-0.9)], low American Spinal Injury Association (ASIA) impairment scale at diagnosis [aHR 0.4 (0.2-0.9)], and thoracic spinal cord compression [aHR 0.2 (0.08-0.5)] were associated with poor outcome. Duration of antibiotic treatment was not associated with functional outcome.SND is more common in cervical, thoracic, and S. aureus PVO, in the presence of epidural abscess, and when CRP >150 mg/L. Although neurological deterioration occurs in 30% of patients in early follow-up, the functional outcome is quite favorable in most cases after 3 months. The precise impact of optimal surgery and/or corticosteroids therapy must be specified by further studies.
[hal-02548927] Nevirapine Use Is Associated with Higher Bone Mineral Density in HIV-1 Positive Subjects on Long-Term Antiretroviral Therapy
Date: 21 4 月 2020 - 10:37
Desc: We assessed bone mineral density (BMD) in a cohort of human immunodeficiency virus (HIV)-positive patients after a median of 11 years of combination antiretroviral therapy (cART) and evaluated the respective role of HIV infection and antiretroviral drugs (ARVs). A cross-sectional study of 162 participants (131 male) from the ANRS-C08 cohort was performed with bone dual-energy X-ray absorptiometry (DXA) scans and renal assessment. The window of exposure to ARVs was defined as an exposure of more than six cumulative months during the last 3 years before the DXA evaluation to account for a cumulative exposure that could affect bone remodeling. The association with low BMD (Z-score < -2) was assessed by a multiple logistic regression model. The study population was 50 years (median), hepatitis C virus (HCV) (18%), and hepatitis B virus (HBV) (8%) coinfection with HIV-RNA <50 c/mL in 89%, median CD4 of 619/mm3. Prevalence of low BMD was 18% in males and 6% in females. The factors associated with a Z-score < -2 in males were uric acid renal loss [adjusted odds ratio (aOR): 6.1; 95% confidence interval (CI): 1.2-31.5; p = .03], HCV coinfection (aOR: 4.0; 95% CI: 1.3-12.2; p = .02), and less frequent window of exposure to nevirapine (NVP) (aOR: 0.1; 95% CI: 0.02-0.6; p = .01). For the full study sample, there was a strong positive association between duration of exposure to NVP and lumbar spine Z-score (p = .004). HIV-positive patients exposed to long-term cART have a high incidence of low BMD. Tenofovir disoproxil fumarate and ritonavir-boosted protease inhibitors did not seem to be associated with increased risk of low BMD, whereas NVP exposure appeared to have an independent positive association.
[hal-03704080] CD4 Cell Count Response to First-Line Combination ART in HIV-2+ Patients Compared with HIV-1+ Patients: A Multinational, Multicohort European Study
Date: 24 6 月 2022 - 16:25
Desc: [...]
[inserm-02068625] Genome sequencing of strains of the most prevalent clonal group of O1:K1:H7 Escherichia coli that causes neonatal meningitis in France
Date: 15 Mar 2019 - 10:18
Desc: BACKGROUND: To describe the temporal dynamics, molecular characterization, clinical and ex vivo virulence of emerging O1:K1 neonatal meningitis Escherichia coli (NMEC) strains of Sequence Type complex (STc) 95 in France. The national reference center collected NMEC strains and performed whole genome sequencing (WGS) of O1:K1 STc95 NMEC strains for phylogenetic and virulence genes content analysis. Data on the clinical and biological features of patients were also collected. Ex vivo virulence was assessed using the Dictyostelium discoideum amoeba model. RESULTS: Among 250 NMEC strains collected between 1998 and 2015, 38 belonged to O1:K1 STc95. This clonal complex was the most frequently collected after 2004, representing up to 25% of NMEC strains in France. Phylogenetic analysis demonstrated that most (74%) belonged to a cluster designated D-1, characterized by the adhesin FimH30. There is no clinical data to suggest that this cluster is more pathogenic than its counterparts, although it is highly predominant and harbors a large repertoire of extraintestinal virulence factors, including a pS88-like plasmid. Ex vivo virulence model showed that this cluster was generally less virulent than STc95 reference strains of O45S88:H7 and O18:H7 serotypes. However, the model showed differences between several subclones, although they harbor the same known virulence determinants. CONCLUSIONS: The emerging clonal group O1:K1 STc95 of NMEC strains is mainly composed of a cluster with many virulence factors but of only moderate virulence. Whether its emergence is due to its ability to colonize the gut thanks to FimH30 or pS88-like plasmid remains to be determined.
[hal-02278657] Initial management of diabetic ketoacidosis and prognosis according to diabetes type: a French multicentre observational retrospective study
Date: 4 9 月 2019 - 15:55
Desc: BACKGROUND: Guidelines for the management of diabetic ketoacidosis (DKA) do not consider the type of underlying diabetes. We aimed to compare the occurrence of metabolic adverse events and the recovery time for DKA according to diabetes type. METHODS: Multicentre retrospective study conducted at five adult intermediate and intensive care units in Paris and its suburbs, France. All patients admitted for DKA between 2013 and 2014 were included. Patients were grouped and compared according to the underlying type of diabetes into three groups: type 1 diabetes, type 2 or secondary diabetes, and DKA as the first presentation of diabetes. Outcomes of interest were the rate of metabolic complications (hypoglycaemia or hypokalaemia) and the recovery time. RESULTS: Of 122 patients, 60 (49.2%) had type 1 diabetes, 28 (22.9%) had type 2 or secondary diabetes and 34 (27.9%) presented with DKA as the first presentation of diabetes (newly diagnosed diabetes). Despite having received lower insulin doses, hypoglycaemia was more frequent in patients with type 1 diabetes (76.9%) than in patients with type 2 or secondary diabetes (50.0%) and in patients with newly diagnosed diabetes (54.6%) (p = 0.026). In contrast, hypokalaemia was more frequent in the latter group (82.4%) than in patients with type 1 diabetes (57.6%) and type 2 or secondary diabetes (51.9%) (p = 0.022). The median recovery times were not significantly different between groups. CONCLUSIONS: Rates of metabolic complications associated with DKA treatment differ significantly according to underlying type of diabetes. Decreasing insulin dose may limit those complications. DKA treatment recommendations should take into account the type of diabetes.
Autres contacts
Hôpital Robert Debré
48, boulevard Sérurier
75935 PARIS CEDEX 19
