Bacterial infectious diseases:  The PG perspective Ivo G Boneca Group Biology and genetics of the bacterial cell wall Inst...
PG a key component of bacterial physiology peptidoglycan Bacterial shape/  physiology Antibiotics  resistance Host/Microbe...
Understanding PG structure and assembly How do they work ? How do they determine shape? Model PBP2 MreC SID 116 226 PBP2 (...
Can the SID peptide be used as an inhibitor ? <ul><li>New therapeutic strategies </li></ul><ul><li>Overcome Resistance mec...
PG is a signaling molecule Homeostasis  Disease  M A G G M A G G dA <ul><li>Adjuvant activity  </li></ul><ul><li>Maturatio...
Understanding PG as a signaling molecule Analysis of the H ost response DNA arrays  Fine analysis of  PG  distribution Str...
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 (0.0...
Perspectives <ul><li>Diagnostics </li></ul><ul><ul><ul><li>sepsis (PG detection) </li></ul></ul></ul><ul><ul><ul><li>steri...
peptidoglycan Bacterial shape/  physiology Antibiotics  resistance Host/Microbe interactions
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1.2 ivo boneca

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1.2 ivo boneca

  1. 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. 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. 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. 4. Can the SID peptide be used as an inhibitor ? <ul><li>New therapeutic strategies </li></ul><ul><li>Overcome Resistance mechanisms </li></ul>SID 116 226 PBP2 (588 aa) N-ter C-ter MreC (248 aa) SP TAT +SID
  5. 5. PG is a signaling molecule Homeostasis Disease M A G G M A G G dA <ul><li>Adjuvant activity </li></ul><ul><li>Maturation of intestinal </li></ul><ul><li>lymphoid tissues </li></ul><ul><li>Activation of </li></ul><ul><li>neutrophils </li></ul><ul><li>Induced slow-wave sleep </li></ul><ul><li>Ex: Streptococcus </li></ul><ul><li>pneumoniae </li></ul><ul><li>Gram-positive septic shock </li></ul><ul><li>Induced arthritis </li></ul><ul><li>Ex: Staphylococcus aureus </li></ul><ul><li>Cytotoxicity </li></ul><ul><li>Ex: Bordetella pertussis </li></ul>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. 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. 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. 8. Perspectives <ul><li>Diagnostics </li></ul><ul><ul><ul><li>sepsis (PG detection) </li></ul></ul></ul><ul><ul><ul><li>sterile inflammation (Arthritis) </li></ul></ul></ul><ul><li>Probiotics ( Macho Fernandez et al. Gut . 2011. Apr 6. [Epub ahead of print]) </li></ul><ul><ul><ul><li>prevention of ulcerative colitis, Crohn’s disease (Nod2) </li></ul></ul></ul><ul><ul><ul><li>enhanced vaccination, etc. (Nod2) </li></ul></ul></ul><ul><li>New innovative treatments </li></ul><ul><ul><ul><li>chronic inflammatory diseases (Nod1) </li></ul></ul></ul><ul><ul><ul><li>cancers associated with chronic inflammation (Nod1) </li></ul></ul></ul><ul><ul><ul><li>against antibiotic resistant bacteria (SID peptide) </li></ul></ul></ul>
  9. 9. peptidoglycan Bacterial shape/ physiology Antibiotics resistance Host/Microbe interactions
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