Xavier Nassif

Website: http://posi-lab.fr

Three main research axes are being pursued.

(i) The first approach focuses on the mechanisms and consequences of the interaction of extra-cellular bacterial pathogens with endothelial cells using Neisseria meningitidis as a paradigm. This pathogen following bloodstream invasion from the nasopharynx establishes a strong interaction with the capillaries. This interaction is associated with the occurrence of meningitis and Purpura fulminans. Our objectives are to provide a coherent picture of meningococcal pathogenesis by dissecting the interaction between meningococci and endothelial cells at the molecular, cellular, and tissular levels.

(ii) The second approach consists in deciphering the molecular bases of the host-pathogen metabolic interplay of an intracellular bacterial pathogen, using Francisella tularensis as a model organism. The virulence of this Gram-negative intracellular bacterium, causative agent of the zoonotic disease tularemia, is tightly linked to its capacity to multiply in the cytosolic compartment of infected macrophages. Our objectives are: i) to understand how the metabolism of this bacteria has evolved to adapt to its intracellular niche; and ii) to define how the metabolism of the host itself is modified in response to the infection.

(iii) The third approach aims at providing new insights on Staphylococcus aureus pathogenesis, which is one of the deadliest bacteria in Western countries. We are particularly committed to the study of virulence factors associated with chronic infections and we have implemented translational research projects involving cohorts of children with chronic S. aureus infections (cystic fibrosis and epidermolysis bullosa). Bacterial adaptation explains why bacteria persist at infected sites despite antibiotic treatment. Our two main objectives are: i) to identify genetic mutations modulating bacterial virulence potential and host responses, through characterization of adapted S. aureus isolates, and ii) to study the impact of S. aureus adaptation in vitro and in vivo, with a focus on the host inflammatory response and cytokine secretion.

Top 5 publications

1. Barnier, JP et al. (2021) The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus. PNAS 2021;118 (45)
2. Le Guennec, L et al. (2020) Receptor recognition by meningococcal type IV pili relies on a specific complex N-glycan. PNAS 2020;117 (5):2606-2612.
3. Virion, Z et al. (2019) Sialic acid mediated mechanical activation of β2 adrenergic receptors by bacterial pili. Nat Commun. 2019;10 (1):4752. doi: 10.1038/s41467-019-12685-6.
4. Tan, X et al. (2019) Chronic Staphylococcus aureus Lung Infection Correlates With Proteogenomic and Metabolic Adaptations Leading to an Increased Intracellular Persistence. Clin Infect Dis. 2019;69 (11):1937-1945
5. Ziveri, J et al. (2017) The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella. Nat Commun. 2017;8 (1):853.

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