Penicillin Resistance Compromises Nod1-Dependent Proinflammatory Activity and Virulence Fitness of Neisseria meningitidis.

Maria Leticia Zarantonelli (1) , Anna Skoczynska (2, 1) , Aude Antignac (1, 3) , Meriem El Ghachi (4, 5) , Ala-Eddine Deghmane (3) , Marek Szatanik (1, 3) , Céline Mulet (6) , Catherine Werts (4, 5) , Lucie Peduto (7, 5) , Martine Fanton d'Andon (4, 5) , Francoise Thouron (8) , Faridabano Nato (9) , Lionel Lebourhis (10) , Dana Philpott (10) , Stephen E. Girardin (6) , Francina Langa Vives (8) , Philippe Sansonetti (6, 11) , Gérard Eberl (7) , Thierry Pedron (12) , Muhamed-Kheir Taha (3, 1) , Ivo Gomperts Boneca (4, 5)

1 Neisseria
2 NRCBM - National Reference Centre for Bacterial Meningitis [Warsaw, Poland]
3 Infections Bactériennes Invasives
4 BGPB - Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall
5 Groupe Avenir
6 Pathogénie Microbienne Moléculaire
7 Développement des Tissus Lymphoïdes
8 CIGM - Centre d'Ingénierie génétique murine - Mouse Genetics Engineering Center
9 Production de Protéines Recombinantes et d'Anticorps (Plate-Forme)
10 Immunité Innée et Signalisation
11 Collège de France - Chaire Microbiologie et Maladies infectieuses
12 Pathogénie Microbienne Moléculaire

Neisseria meningitidis is a life-threatening human bacterial pathogen responsible for pneumonia, sepsis, and meningitis. Meningococcal strains with reduced susceptibility to penicillin G (Pen(I)) carry a mutated penicillin-binding protein (PBP2) resulting in a modified peptidoglycan structure. Despite their antibiotic resistance, Pen(I) strains have failed to expand clonally. We analyzed the biological consequences of PBP2 alteration among clinical meningococcal strains and found that peptidoglycan modifications of the Pen(I) strain resulted in diminished in vitro Nod1-dependent proinflammatory activity. In an influenza virus-meningococcal sequential mouse model mimicking human disease, wild-type meningococci induced a Nod1-dependent inflammatory response, colonizing the lungs and surviving in the blood. In contrast, isogenic Pen(I) strains were attenuated for such response and were out-competed by meningococci sensitive to penicillin G. Our results suggest that antibiotic resistance imposes a cost to the success of the pathogen and may potentially explain the lack of clonal expansion of Pen(I) strains.

Domaines: Santé publique et épidémiologie; Bactériologie

Maria Leticia Zarantonelli, Anna Skoczynska, Aude Antignac, Meriem El Ghachi, Ala-Eddine Deghmane, et al.. Penicillin Resistance Compromises Nod1-Dependent Proinflammatory Activity and Virulence Fitness of Neisseria meningitidis.. Cell Host and Microbe, 2013, 13 (6), pp.735-745. ⟨10.1016/j.chom.2013.04.016⟩. ⟨pasteur-02088904⟩