抗生素作用的病理生理学Huntingintracellular bacteria with .pptVIP

Karmanshah, Iran, 24 May 2011 1st International and 12th Iranian Congress of Microbiology Hunting intracellular bacteria with antibiotics Paul M. Tulkens, MD, PhD Cellular and Molecular Pharmacology Unit Centre for Clinical PharmacyLouvain Drug Research Institute Catholic University of Louvain,Brussels, Belgium But before that, where are you from ? Intracellular infection: bacterial strategies Intracellular infection and recurrence/relapses: the case of S. aureus (as an example) Intracellular infection and recurrence/relapses: the case of S. aureus (as an example) A real need... Settting up the model … S. aureus virulence factors S. aureus virulence factors Staphyloxanthinsynthesis Our material…. The results…. And with other strains…. Antibiotics and intracellular infection… ?-lactams: a pharmacokinetic paradox ??-lactams and S. aureus... (MSSA) The intracellular pharmacodynamic paradox of ?-lactams… Back to the future… Biochemistry comes to your help… Acid pH favors penicillin binding to PBP2a Acid pH favors oxacillin-induced conformational change in PBP2a Screening available antibiotics New glycopeptides (oritavancin,telavancin, dalbavancin)… Telavancin (and oritavancin) new modes of action … Telavancin … Telavancin intracellular accumulation and subcellular disposition Intracellular activity of telavancin vs. vancomycin:? MSSA? MRSA Intracellular activity of telavancin vs. vancomycin:? VISA? VRSA Telavancin intracellular activity in comparison with other drugs… SCVs of S. aureus as a cause of persistent foreign body infection Intracellular SCVs… Intracellular SCVs and antibiotics … Will this be successful ? And now Listeria… As if you were there … A surprise … A potential explanation … through proteomics What may change in intracellular Listeria… In a nutshell intracellular bacteria is a reality… antivirulence therapy is a nice project … most available antibiotics are poorly active against intracellular bacteria, …and if they are, they most