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1.2 ivo boneca
1.2 ivo boneca
1.2 ivo boneca
1.2 ivo boneca
1.2 ivo boneca
1.2 ivo boneca
1.2 ivo boneca
1.2 ivo boneca
1.2 ivo boneca
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1.2 ivo boneca

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  • 1. Bacterial infectious diseases: The PG perspective Ivo G Boneca Group Biology and genetics of the bacterial cell wall Institut Pasteur, INSERM Paris, France CEA CHRU CNRS CPU INRA INRIA INSERM INSTITUT PASTEUR IRD
  • 2. PG a key component of bacterial physiology peptidoglycan Bacterial shape/ physiology Antibiotics resistance Host/Microbe interactions Mesenteric Lymph Nodes Peyer’s Patches Cryptopatches Lymphatics ILFs Gram -
  • 3. Understanding PG structure and assembly How do they work ? How do they determine shape? Model PBP2 MreC SID 116 226 PBP2 (588 aa) N-ter C-ter MreC (248 aa)
  • 4. Can the SID peptide be used as an inhibitor ?
    • New therapeutic strategies
    • Overcome Resistance mechanisms
    SID 116 226 PBP2 (588 aa) N-ter C-ter MreC (248 aa) SP TAT +SID
  • 5. PG is a signaling molecule Homeostasis Disease M A G G M A G G dA
    • Adjuvant activity
    • Maturation of intestinal
    • lymphoid tissues
    • Activation of
    • neutrophils
    • Induced slow-wave sleep
    • Ex: Streptococcus
    • pneumoniae
    • Gram-positive septic shock
    • Induced arthritis
    • Ex: Staphylococcus aureus
    • Cytotoxicity
    • Ex: Bordetella pertussis
    Girardin et al. 2003. J. Biol. Chem . 278(11):8869-72 Girardin et al. 2003. J. Biol. Chem . 278(43):41702-8 Girardin et al. 2003. Science . 300(5625):1584-7 Nod1 Nod2 NF-kB JNK MAMP Intracellular Nod1
  • 6. Understanding PG as a signaling molecule Analysis of the H ost response DNA arrays Fine analysis of PG distribution Structural analysis of circulating 3 H- PG by HPLC Analysis of circulating cells carrying 3 H- PG by AutoMACs Soluble 3 H-PG Homeostasis vs Disease (IBD, sepsis)
  • 7. Studying the PG as a signaling molecule in vivo time 24 h Femur (0.02 cpm/mm 2 ) Stomach (0.24 cpm/mm 2 ) Intestin (0.08 cpm/mm 2 ) 1 h 6 h
  • 8. Perspectives
    • Diagnostics
        • sepsis (PG detection)
        • sterile inflammation (Arthritis)
    • Probiotics ( Macho Fernandez et al. Gut . 2011. Apr 6. [Epub ahead of print])
        • prevention of ulcerative colitis, Crohn’s disease (Nod2)
        • enhanced vaccination, etc. (Nod2)
    • New innovative treatments
        • chronic inflammatory diseases (Nod1)
        • cancers associated with chronic inflammation (Nod1)
        • against antibiotic resistant bacteria (SID peptide)
  • 9. peptidoglycan Bacterial shape/ physiology Antibiotics resistance Host/Microbe interactions

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