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Action Et Contrôle Des Leucotoxines De Staphylococcus Aureus Sur Les Cellules Cibles Mira Tawk

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Action Et Contrôle Des Leucotoxines De Staphylococcus Aureus Sur Les Cellules Cibles Mira Tawk Action et contrôle des leucotoxines de Staphylococcus aureus sur les cellules cibles Mira Tawk To cite this version: Mira Tawk. Action et contrôle des leucotoxines de Staphylococcus aureus sur les cellules cibles. Bactériologie. Université de Strasbourg, 2014. Français. NNT : 2014STRAJ111. tel-01234206 HAL Id: tel-01234206 https://tel.archives-ouvertes.fr/tel-01234206 Submitted on 26 Nov 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ DE STRASBOURG ÉCOLE DOCTORALE DES SCIENCES DE LA VIE ET DE LA SANTE EA-7290 Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë THÈSE présentée par : Mira TAWK soutenue le : 07 juillet 2014 pour obtenir le grade de : !"#$%&'($')R%+,-$&.,# '($'0#&1.2!%&3 Discipline/ Spécialité : V'# #2 S,2M A1.#!21 M-*M!3*'0#1 #2 C#**3*'0#1 "# * B'-*-%'# Action et contrôle des leucotoxines de Staphylococcus aureus sur les cellules cibles THÈSE dirigée par : Dr. PRÉVOST Gilles MCU-PH, Université de Strasbourg Pr. BOURCIER Tristan Professeur, Université de Strasbourg RAPPORTEURS : Pr. FREY Joachim PR-PUPH, Université de Berne Dr. LADANT Daniel DR, Institut Pasteur-Paris AUTRES MEMBRES DU JURY : Dr. FAFI-KREMER Samira MCU-PH, Université de Strasbourg Dr. JOUBERT Olivier MCU, Université de Lorraine TAWK Mira · [email protected] Université de Strasbourg · EA-7290 Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë Institut de Bactériologie de la Faculté de Médecine · 3 rue Koeberlé · 67000 Strasbourg · FRANCE '' I !"#$%&!'("G Remerciements Je (*!'"##&! !&,*!&#-!#.&/#01%,2* #3456#!(#-!#7&/#7%'*!-#8979:;#<S%>1*&#%,,!$( # de juger ce travail, ainsi que le Dr. Samira FAFI-KRAEMER et le Dr. Olivier JOUBERT pour avoir accept de faire partie du jury. Toute ma gratitude Gilles PRVOST $1@&# %>1*&# <*&*A # ,!((!# (2 "!# !(# S%>1*&# permis de la r aliser dans les meilleures conditions. Merci pour tous les efforts qui 1'(# $!& *"# <!# C*'%',!&# ,!((!# (2 "!D# ,!# E@*# 'S%# $%"# (1@F1@&"# ( # C%, ile. Merci de S%>1*&#1CC!&(# des opportunit s de communications, de collaborations et de projets. Je tiens particuli rement lui exprimer ma gratitude pour son soutien et surtout pour (1@"#-!"#<1,@ !'("#%< *'*"(&%(*C"#E@S*-#%#<@# !#C%*&!/# 0S!"$ &!#%>1*&# t digne de la ,1'C*%',!# E@S*-# S%# %,,1&< !# !(# E@!# ,!# (&%>%*-# soit finalement la hauteur de ses esp rances. Merci au Pr. Tristan BOURCIER pour avoir co-encadr ma th se et pour le financement travers la Bourse Berthe FOUASSIER. Je remercie norm ment Emmanuel JOVER pour sa disponibilit . Je le remercie pour mon initiation la microscopie confocale et ses nouvelles id es de manipes. Je le &! !&,*!# A%-! !'(#$1@&#'1"#<*",@""*1'"#E@*# S1'(#G!%@,1@$#!'&*,2* et pour tous les conseils E@S*-# S%#$&1<*A@ / Je remercie Cristina POTRICH et Mauro DALLA SERRA pour leur gentillesse et (1@(# ,!# E@S*-"# S1'(# %$$&*"# "@&# -!"# ! G&%'!"# "H'(2 (*E@!"/# IS (%*(# @'# $-%*"*&# <!# travailler avec eux. Merci galement Mauro pour son accueil Trento, et tout ce E@S*-#%#C%*(#$1@&# e faciliter mon s jour. Je remercie Zouhair ASFARI pour la synth se des calixar nes et sa disponibilit . Je remercie galement nos collaborateurs de -SJ.KI : Sarah CIANFERANI et Fran ois DEBAENE pour leur travail sur les calixar nes. 4 Merci nos ,1--%G1&%(!@&"# <!# -S Institut de Pharmacologie et Biologie Structurale (IPBS) de Toulouse : Lionel Mourey et Laurent Maveyraud, qui ont contribu ce travail. Merci 7%'*!--%# L5449# <!# S%>1*&# *'*(* # # -%# %'*$@-%(*1'# <!"# H!@M# <!# -%$*'"D# surtout la conse &>%(*1'#!(##-%#,1@$!/#N!&,*# A%-! !'(##-S E@*$!#<!#7%>*<#KJIOP# E@*# S%#$!& *"#<S@(*-*"!&#"1'#,&H1"(%(/# Je remercie Jean-Michel SCHEFFTEL !(# 3& < &*,# PIK49NN# E@*# S1'(# <1'' # -S1$$1&(@'*( #<!#C%*&!#-!# 1'*(1&%(#<!#;&%>%@M#.&%(*E@!"#<!#Q%,( &*1-1A*!/# Un g &%'<# !&,*# # -S Unit Inserm U1110 (Institut de Virologie, Strasbourg) : M lanie, Sylvie, Thomas, Bin et les autres qui nous ont c d les PMNs de leurs E Buffy coats F. Cette th se a t soutenue par la fondation de France N Bourse Berthe FOUASSIER, par @'!#G1@&"!#<!#-%#4 A*1'#9-"%,!#!(#$%&#-S59 -STUV#<!#-SW'*>!&"*( #<!#P(&%"G1@&A/ 0!#&! !&,*!#-S!'"! G-!#<@#$!&"1''!-#<!#-SJ'"(*(@(#<!#Q%,( &*1-1A*!# Un grand merci Daniel KELLER, pour sa disponibilit , pour son savoir faire technique et pour son aide dans la recherche des solutions tous les probl mes. 0!# (*!'"# # !M$&* !&# %# A&%(*(@<!# !'>!&"# 4%H 1'<!# XJ4947Y;D# <S%G1&<# $1@&# "1'# savoir faire technique et son aide dans les manipes, puis, et surtout, pour ses qualit s 2@ %*'!"/#N!&,*#<!# S%>1*&#C%*(#< ,1@>&*&#-S9-"%,!#!(#<S%>1*&#!""%H #<!# S%$$&!'<&!# -S%-"%,*!'# Z !# "*# 1'# 'S%# $%"# !@# -!# (! $"# <!# (&1$# %>%',!&\/# N!&,*# $1@&# "%# G1''!# humeur et les gteaux lors des pauses quotidiennes avant son d part, et le E ravitaillement F lors de ses visites actuelles. Je remercie les th sards qui taient au labo mon arriv e, Benot-Joseph, Wardi, P1$2*!#!(#O2%-<1@'#E@*# S1'(#$!& *"#@'!#(& "#&%$*<!#*'( A&%(*1'#<%'"#-%#>*!#<@#-%G1/# Je remercie Galle pour sa serviabilit , sa gentillesse et surtout pour sa bonne humeur et les moments de rigolade. Je la remercie galement pour sa contribution aux manipes. Je remercie aussi les nouveaux th sards, lodie et Xavier pour -S% G*%',!#%@#-%G1#!(#-!"#$%@"!"#<!# *<*/# Je remercie Pauline pour son amiti . 4' Merci tous mes amis qui S1'(# %*< # # $%""!&# ,!"# "!$(# %'"# <!$@*"# 1'# %&&*> !# !'# France et E@*# S1'(#$!& *"#<S1@G-*!&# 1 !'(%' !'(# le travail. Elie, mon meilleur % *D# %>!,# E@*# FS%*# $%"" # -%# $-@$%&(# <!# 1'# (! $"# !(# %>!,# E@*# FS%*# $%&(%A # ,!((!# exp rience. Patrick, Ranine, Omar, Marianne, Ahmad, Ricardos pour leur pr sence, les sorties, les repas, les voyages que nous avons effectu ensemble... Laurent D., 8%@&!'(#./D#0 & HD#N%( #!(#-!"# %@(&!"# %>!,#E@*#FS%*#< ,1@>!&(#@'#%@(&!# 1'<!/#0!# pense aussi Nisrine et Zeina avec qui je suis rest e en contact malgr la distance qui nous s pare. Enfin, je remercie ma grande famille pour son soutien et son amour. Farid et N1'*E@!#$1@&# S%>1*&#2 G!&A !#$!'<%'(# !"#$&! * &!"#%'' !"##P(&%"G1@&A/#P% mira et Samia pour leur soutien inconditionnel. X!1&A!"D# 9<<*"" # !(# (1@"# -!"# %@(&!"G# 0!# remercie surtout mon p re et ma m re, autant pour leur soutien financier que pour leur soutien moral et leurs encouragements pendant les moments les plus durs. 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