Conf 1 - IOA Physiopath DESC jpb 20 09 18 · 2018-10-09 · Title: Microsoft PowerPoint - Conf 1 -...
Transcript of Conf 1 - IOA Physiopath DESC jpb 20 09 18 · 2018-10-09 · Title: Microsoft PowerPoint - Conf 1 -...
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Physiopathologie des infections osseuses chroniques(biofilm, persistance intra-cellulaire)
JP BruMaladies Infectieuses
Centre Hospitalier Annecy Genevois
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Bactérie
Os / matériel HôteRéponse immune
InoculationInfection aiguëDestruction osseusePersistance bactérienne
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InoculationInfection aiguëDestruction osseusePersistance bactérienne
Comportement bactérien
Conséquences pour infections osseuses / sur matériel
(évolutives et thérapeutiques)
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1/ Adhérence etorganisations bactériennes
2/ Variants microcolonies
3/ Persistance intra cellulaire
Microcolonies formant biofilm identifiées :• 3.3–3.4 milliard d’années South African Kornberg formation• 3.2-milliard d’années deep-sea hydrothermal rocks of the Pilbara Craton, Australia
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Adhérence
Cécile Berne NATURE Reviews | Microobiologyvolume 16 | OCTOBER 2018 | 617
Gristina AG: Science 237:1588-1595, 1987
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Adhérence
Cécile BerneNATURE Reviews | Microobiologyvolume 16 | OCTOBER 2018 | 617
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Adhérence & organisation bactérienne
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Interaction hydrophobiqueForces électrostatiquesForces de Van der Wals
Fibrinogènefacteur de WillbrandPlaquettes prothrombine
Adhérence & organisation bactérienne
European cells & Materials Vol 8 2004 p 37-57
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Formation du biofilm
European cells & Materials Vol 8 2004 p 37-57
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Formation du biofilm
European cells & Materials Vol 8 2004 p 37-57
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polysaccharide intercellular adhesion (PIA) exopolysaccharide,proteins such as accumulation-associated protein (Aap)extracellular matrix binding protein (Embp),teichoic acids, extracellular DNA (eDNA).Channels in the biofilm are formed by Phenol-soluble modulins (PSMs),
Matrice du biofilm
Front. Microbiol. February 2018 | Volume 9 | Article 359
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Nature reviews microbiology 2004
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• Apporte un environnement stable pour la pousse bactérienne • Favorise les échanges entre bactéries• Stabilise la colonie bactérienne à la surface du substrat
Biofilm rôle
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D’après Keith Kasnot, Scientific American 2001
Résistance auxagressions physicochimique
Micro colonies - BiofilmCommunauté bactérienne
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• Apporte un environnement stable pour la pousse bactérienne • Favorise les échanges entre bactéries• Stabilise la colonie bactérienne à la surface du substrat• Protège d’une grande variété d’agressions possibles:
• Exposition aux UV• toxicité du métal • exposition acide • Déshydratation• substances toxiques
Biofilm rôle
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D’après Keith Kasnot, Scientific American 2001
Résistance auxagressions physicochimique
Protection contre les mécanismes de l’immunité
Micro colonies - BiofilmCommunauté bactérienne
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Front. Microbiol. February 2018 | Volume 9 | Article 359
Biofilm et immunologie
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D’après Keith Kasnot, Scientific American 2001
Résistance auxagressions physicochimique
Modifications ducomportement bactérien
Protection contre les mécanismes de l’immunité
Micro colonies - BiofilmCommunauté bactérienne
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Biofilm modification du comportement bactérien. Phase stationnaire de croissance
Ralentissement métabolique
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A. F. Widmer, The Journal of Infectious Diseases 1990;162:96-102
Biofilm modification du comportement bactérien. Phase stationnaire de croissance
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A. F. Widmer, The Journal of Infectious Diseases 1990;162:96-102
Staphylococcus epidermidis B3972 Producteur de Slime.
CroissanceLogarith-mique
Croissancestationnaire
ATBContrôle
ATBContrôle
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Nature /scientific report2016 DOI: 10.1038/srep29707
Biofilm modification du comportement bactérien. Phase stationnaire de croissance
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Infection de matériel étranger Efficacité des antibiotiques. Modèles animaux
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Efficacy of Daptomycin inImplant-Associated Infection Due to Methicillin-ResistantStaphylococcusaureus : Importance of Combination with Rifampicin
Antimicrob. Agents Chemother,July 2009, p. 2719–2724
*P 0.05; **P 0.01; ***P 0.001.
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Infections de Prothèsesarticulaires à S. aureus.Efficacité selon les ATB
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E Senneville Clinical Infectious Diseases 2011;53(4):334–340
Infections de Prothèses articulaires à S. aureus. Efficacité selon les ATB
Rifamp - Fluoroquinolone
Autres antibiotiques
p.003
98 Pts
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Archives of Orthopaedic and Trauma Surgery oct 2017 doi10.1007/s00402-018-2886-0
ATB actif dans biofilm
Pas d’ ATB actif dans biofilm
Infections de Prothèses articulaires. Efficacité selon les ATB
163 Pts
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Archives of Orthopaedic and Trauma Surgery oct 2017 doi10.1007/s00402-018-2886-0
Infections de Prothèses articulaires. Efficacité selon les ATB
ATB actif dans biofilmPas d’ ATB actifdans biofilm
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1/ Adhérence etorganisations bactériennes
2/ Variants microcolonies
3/ Persistance intra cellulaire
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Small Colony Variants
Nat Rev Microbiol 2006(4)295
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Small Colony Variants
Nat Rev Microbiol 2006(4)295
Déficit en transport d’électronAltération de synthèse de medianone& hémine
Déficit en biosynthèse de thymidine
Phénomène d’adaptation auxotrophique
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Small Colony Variants
Nat Rev Microbiol 2006(4)295
S. Aureus normalSCV SCV
Modifications phénotypiques
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Small Colony Variants
Nat Rev Microbiol 2006(4)295
Petites colonies
Pousse lente
Activité oxydatives / métaboliques
Capacités d’adhérence
Production de certains facteurs de virulence
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Small Colony Variants
Sendi Clinical Infectious Diseases 2006;43:961–7
Petites coloniesPousse lenteActivité oxydatives / métaboliquesCapacités d’adhérenceProduction de certains facteurde virulence
fibroblastes
SCVFacilitation de la persistance intracellulaire
Uprégulation des gènes de persistance
Uprégulation des gène de formation du biofilm
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Small Colony VariantsPetites coloniesPousse lenteActivité oxydatives / métaboliquesCapacités d’adhérenceProduction de certains facteurde virulence
Uprégulation des gènes de persistance
Uprégulation des gène de formation du biofilm
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Small Colony Variants
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Small Colony Variants relation avec les antibiotiques
Résistance par mécanisme spécifique décrite pour fluoroquinolones, aminosides, Co trimoxazole
Induction de formation de SCV par exposition àCo-trimoxazole, fluoroquinolone
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Small Colony Variants Sensibilité AntibiotiquesClinical Characteristics and Outcomes of Prosthetic Joint Infection Caused by Small Colony Variant Staphylococci
Tande et al Mbio 2014
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Small Colony Variants Sensibilité Antibiotiques
10 souches S.aureus Paires de SCV & souche parentAAC2018 62 Issue 4
cc
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Small Colony Variants Sensibilité Antibiotiques
10 souches S.aureuscPaires de SCVc& souche parentAAC2018 62 Issue 4
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Small Colony Variants conséquences IOA
Tande et al Mbio 2014
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Tande et al Mbio 2014
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Tande et al Mbio 2014
P 0.51
Remplacement prothétique en 2 temps 100 % des patients
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Small Colony Variants : bactéries pour lesquelles des phénotypes SCV ont été décrits
Staphylococcus aureusStaphylococcus coagulase négativePseudomonas aeruginosaE. coli,N. GonorrhoeaeS. Typhimurium ShigellaProteus sp., Klebsiella pneumoniae, Providencia stuartii, Enterobacter cloacae, S. marcescens, Citrobacter freundii
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1/ Adhérence etorganisations bactériennes
2/ Variants microcolonies
3/ Persistance intra cellulaire
Microcolonies formant biofilm identifiées :• 3.3–3.4 milliard d’années South African Kornberg formation• 3.2-milliard d’années deep-sea hydrothermal rocks of the Pilbara Craton, Australia
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Persistance intracellulaire
Internalisation dans les cellules non phagocytaires
Persistance intracellulaire
Échappement du compartiment intra cellulaire
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Persistance intracellulaire
Internalisation dans les cellules non phagocytaires
FibroblastesCellules endothélialesOstéoblasteskératinocytes
Frontiers in Cellular and Infection MicrobiologyApril 2012 | Volume 2 | Article 43 | 1
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Persistance intracellulaire
Frontiers in MicrobiologyJuly 2017Volume 8 | Article 1354
C vivantes
C mortes
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Persistance intracellulaire
Frontiers in Microbiology July 2017 Volume 8 | Article 1354
SCV
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Persistance intracellulaire
Frontiers in Microbiology July 2017 Volume 8 | Article 1354
Échappement du compartimentintra cellulaire
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Persistance intracellulaire
Rat boneInoculation 106 osteoblasts infectedwith 106 CFU intra- cellular S. aureus
Day 21
106 CFU/mL
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Persistance intracellulaire Antibiotiques actifs
F. Valour Antimicrob Agents Chemother 201559:2029 –2036.
Antimicrobial Activity against Intraosteoblastic Staphylococcus aureus
Inoculum intraostéoblastique
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1/ Adhérence etorganisations bactériennes
2/ Variants microcolonies
3/ Persistance intra cellulaire
Merci de votre attention