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Intitulé du sujet: Identification of bacterial determinants of host responses to chronic Staphylococcus aureus infections

Sujet

Codirection: non

Nombre de mois: 48 mois

Ecole Doctorale: ED 562 - Bio Sorbonne Paris Cité

Unité de recherche et équipe:

INSTITUT NECKER ENFANTS MALADES

INSERM U1151 - CNRS UMR 8253

Université PARIS CITE UMR_S 1151

Team 7: Host Pathogen Integrative Biology

Coordonnées de l’équipe:

160 rue de Vaugirard 75015 PARIS

Secteur: Sciences de la vie / Life Sciences

Langue attendue: Anglais

Niveau de langue attendu: C2

Description

Description du sujet:

Staphylococcus aureus is a host-associated bacterium, which primarily parasitizes asymptomatically human anterior nares of a third of healthy individuals. S. aureus is also an opportunistic pathogen causing symptomatic infections ranging from superficial skin and soft tissue infections to life-threatening invasive diseases. After an acute inflammatory phase, S. aureus infections can become chronic due to impaired elimination by the host. S. aureus is a leading pathogen associated with chronic infections and is able to establish long-lasting infections of skin or lung in patients, while its exact contribution to disease severity remains elusive.

S. aureus adaptation to chronic infection has been shown to correlate with the accumulation of genomic modifications altering its metabolism, and the expression of multiple virulence genes. Our preliminary results showed that pathoadaptive strategies deployed by S. aureus could directly contribute to disease progression, challenging the common assumption of bacterial adaptation leading to virulence attenuation.

Our general aim is to address the following key questions: What are the typical virulence trajectories in chronic infections? What are the deleterious consequences of bacterial adaptation for the host?

This project will leverage patient cohort and strain collection of patients managed in our children Hospital. This project will combine multi-omic analyses, bacterial phenotypic profiling, innovative in vitro and in vivo models with direct assessment of the consequences of chronic infections on surrounding microbiota and on the immune response through longitudinal follow-up of patients to provide a comprehensive view of S. aureus virulence.

To achieve this ambitious PhD program, the applicant will be supported by a scientific team, expert in microbial pathogenesis, mastering all the required state of the art technologies, in an Institute equipped with all the facilities. This project will benefit from very solid preliminary data previously obtained by our team and its collaborators. Team 7 is tightly associated with the Microbiology laboratory of Necker Hospital and collaborates with the clinical departments at the Necker-Enfants Malades Hospital.

Compétences requises:

Knowledge of english

Knowledge of bacterial physiology

Knowledge of molecular biology

Références bibliographiques:

Ramond E, Lepissier A, Ding X, Bouvier C, Tan X, Euphrasie D, Monbernard P, Dupuis M, Saubamea B, Nemazanyy I, Nassif X, Ferroni A, Sermet-Gaudelus I, Charbit A, Coureuil M, Jamet A. Lung-adapted Staphylococcus aureus isolates with dysfunctional agr system trigger a proinflammatory response. The Journal of infectious diseases 2022. DOI: 10.1093/infdis/jiac191.

 

Tan X, Coureuil M, Charbit A, Jamet A. Multitasking Actors of Staphylococcus aureus Metabolism and Virulence. Trends in microbiology 2020;28(1):6-9. DOI: 10.1016/j.tim.2019.10.013.

 

Tan X, Coureuil M, Ramond E, Euphrasie D, Dupuis M, Tros F, Meyer J, Nemazanyy I, Chhuon C, Guerrera IC, Ferroni A, Sermet-Gaudelus I, Nassif X, Charbit A, Jamet A. Chronic Staphylococcus aureus Lung Infection Correlates With Proteogenomic and Metabolic Adaptations Leading to an Increased Intracellular Persistence. Clinical infectious diseases  2019;69(11):1937-1945. DOI: 10.1093/cid/ciz106.

 

Ding X, Robbe-Masselot C, Fu X, Leonard R, Marsac B, Dauriat CJG, Lepissier A, Rytter H, Ramond E, Dupuis M, Euphrasie D, Dubail I, Schimmich C, Qin X, Parraga J, Leite-de-Moraes M, Ferroni A, Chassaing B, Sermet-Gaudelus I, Charbit A, Coureuil M, Jamet A. Airway environment drives the selection of quorum sensing mutants and promote Staphylococcus aureus chronic lifestyle. Nat Commun 2023;14(1):8135. DOI: 10.1038/s41467-023-43863-2.