STANBUL TEKNIK NIVERSITESI MOLEKLER BIYOLOJI VE GENETIK BIYOTEKNOLOJI
İSTANBUL TEKNIK ÜNIVERSITESI MOLEKÜLER BIYOLOJI VE GENETIK &BIYOTEKNOLOJI QUORUM SENSING ODAKLı YENILIKLER VE BIYOTEKNOLOJIK UYGULAMALAR MBG 617 BIYOTEKNOLOJIDE SON GELIŞMELER Hazırlayan : Murat Kemal AVCI Öğretim Üyesi : Doç. Dr. Zeynep Petek ÇAKAR Aralık-2009 Maslak
İÇERIK… Quorum sensing mekanizması. . . Araştırma alanları. . . Günümüzdeki uygulamalar ve potansiyeller. . Sonuç ve Öneriler… 02. 12. 2009 2 Murat Kemal AVCI_İTÜ_MOBGAM www. quorumsensing. net
1. MIKROORGANIZMALAR VE BIZ. . . 02. 12. 2009 ? 3 Murat Kemal AVCI_İTÜ_MOBGAM www. quorumsensing. net
Vücudumuzdaki Mikroorganizma habitatları: 1. Baş derisi 02. 12. 2009 2. Göz 3. Kulak 4. Ağız 5. Deri - Göğüs - Kollar - Eller - Bacaklar - Ayaklar 6. İç organlar - Mide - Barsaklar 5 VS. . Murat Kemal AVCI_İTÜ_MOBGAM www. quorumsensing. net
İnsanları Etkileyen Diğer Faktörlerle Mikroorganizmaların Etkileşimleri 02. 12. 2009 6 Murat Kemal AVCI_İTÜ_MOBGAM www. quorumsensing. net
SONUÇ OLARAK. . İLIŞKININ YÖNLENDIRILMESI. . . 02. 12. 2009 Bir ETKİLEŞİM-İLİŞKİ mevcut. . Tatlı dil. . . . . (Atasözü) Mikroorganizmaların Dili. . . QUORUM SENSİNG (BAKTERİCE) Murat Kemal AVCI_İTÜ_MOBGAM 7 www. quorumsensing. net
QUORUM SENSING 02. 12. 2009 Mikroorganizmaların, ortamdaki hücre konsantrasyonuna bağlı olarak bir takım sinyal molekülleri aracılığıyla aralarında iletişim kurup, davranışlarını/gen ifadelerini populasyon çapında düzenlemelerini sağlayan bir iletişim mekanizmasıdır. Quorum : Yeterli sayı Sense : Hissetmek, algılamak Murat Kemal AVCI_İTÜ_MOBGAM 8 www. quorumsensing. net
QUORUM SENSING 02. 12. 2009 “BAKTERİCE” Sözcükler = Kimyasal Moleküller (Autoinducer Peptides, AIPs) Türe özgü davranış (FENOTİP) - Biyofilm oluşumu - Ekstraselüler enzim üretimi - Toksin salgılama - Antibiyotik üretimi - Kommensal-Patojen Dönüşümü v. . . s. . . 9 Murat Kemal AVCI_İTÜ_MOBGAM www. quorumsensing. net
1980 DEN GÜNÜMÜZE. . QUORUM SENSİNG LİTERATURE in SCİENCEDIRECT from 1980 to 2010 1987 1988 1989 2 1989 1990 5 1990 1991 5 1991 1992 1993 1994 5 1994 1995 8 1995 1996 26 1997 42 1997 1998 71 1998 1999 117 1999 2000 172 2000 2001 238 2001 2002 330 2002 2003 427 2003 2004 494 2005 573 2005 2006 673 2006 2007 736 2007 2008 815 2008 2009 444 2009 2010 594 KARMA TOPLAM : 5789 TOPLAM : 3194 Murat Kemal AVCI_İTÜ_MOBGAM 600 500 400 300 200 100 0 2009 2 2007 3 1987 2005 1986 2003 1985 700 2001 2 1999 1985 1997 1984 1995 o 1993 1 1984 1991 1983 1989 1982 800 1987 1 1985 1982 02. 12. 2009 0 1981 1983 YAYIN SAYISI 1981 YILLAR 1980 0 1 1 o 2 3 2 1 2 5 5 1 1 5 8 26 42 71 117 172 238 330 427. . . 10 www. quorumsensing. net
MEKANIZMANıN TEMEL ELEMANLARı. . . Sinyal Molekülleri - AHL türevleri - Oligopeptitler - Furan türevleri Genler Algılama sistemleri - Gram (-) - Gram (+) Preoteinler Davranış/Fenotip/Ürün Murat Kemal AVCI_İTÜ_MOBGAM 02. 12. 2009 Mikroorganizma Türleri - Bakteriler - Algler - Mayalar - Küfler - Protistler 11 www. quorumsensing. net
MADALYONUN [YOĞUNLUĞA BAĞLI] İKI YÜZÜ. . . Patojen Duyarlı Dirençli A ürünü B ürünü 02. 12. 2009 Kommensal OD 600 t 3 t 2 X formu Y ürünü Masum Canavar Dost Düşman t 1 Eksponansiyal Faz QS Zaman 12 Murat Kemal AVCI_İTÜ_MOBGAM www. quorumsensing. net
DAVRANıŞıN MOLEKÜLER KONTROLÜNE BIR ÖRNEK. . . 02. 12. 2009 ORGANİZMA : Staphylococcus epidermidis Staphylococcus aureus GEN : agr. A, agr. C, agr. D, agr. B (agr operonu) PROTEİNLER : Agr. A, Agr. C, Agr. D, Agr. B, delta toksin ALGILAMA SİSTEMİ : İki bileşenli algılama sistemi FENOTİP/ÜRÜN : Kommensal-Patojen dönüşümü/Toksin Üretimi/Biyofilm oluşumu Murat Kemal AVCI_İTÜ_MOBGAM 13 www. quorumsensing. net
02. 12. 2009 Şekil : Staphylococcal agr sistemi. A) İki ayrı promotor (P 2 ve p 3) ve bunların transkriptleri. P 2 operonu 4 gen içeri; agr. A, B, C ve D. B) Agr D’nin açık yapısında autoinducer peptidin (AIP) amino asit dizisi görülmektedir (koyu harfler). Bu peptid Agr. C’ye bağlanarak metabolik yolun aktivasyonunu sağlayan ligand olarak iş görür. C) Agr. Cnin açık yapısında beş transmembran heliksi görülmektedir. S 9 -rf 1/52 Murat Kemal AVCI_İTÜ_MOBGAM 14 www. quorumsensing. net
12. 05. 2006 15 Şekil. : Staphylococ’larda accessory gene regulator (agr) sistemi. P 2 promotoru sinyal mekanizmasını kodlar (RNAII aracılığıyla) P 3 promotoru ise agr lokusunun effektörü olarak hareket eder (RNAIII tarafından kodlanır). [J. M. Yarwood and P. M. Schlievert, The Journal of Clinical Investigation, December 2003, Volume 112, Number 11] Murat Kemal AVCI_İTÜ_MOBGAM 15 www. quorumsensing. net
AGR SISTEMI INAKTIF OLDUĞUNDA - Protein A 12. 05. 2006 - Koagülaz Virülans Faktörleri - Fibronektin bağlanma proteini vs… (Ekzo proteinler) 16 Hücre duvarıyla ilişkili proteinler (+) ETKİ (-) - Alfa-toksin - Beta toksin - Delta toksin - Serin proteaz - DNAase - Fibrinolizin - Enterotoksin B - TSST-1 Şekil : Agr sisteminin inaktif olması kommensal olmayı teşvik eder. [Yarwood and Schlievert (2003)’den uarlanmıştır, Çizim: M. K. AVCI] Murat Kemal AVCI_İTÜ_MOBGAM 16 www. quorumsensing. net
AGR SISTEMI AKTIF OLDUĞUNDA 12. 05. 2006 - Alfa-toksin - Beta toksin - Delta toksin - Serin proteaz - DNAase - Fibrinolizin - Enterotoksin B - TSST-1 Hücre duvarıyla ilişkili proteinler 17 - Protein A - Koagülaz Virülans Faktörleri - Fibronektin bağlanma proteini vs… (Ekzo proteinler) (-) ETKİ (+) Şekil. 20 : Agr sisteminin aktif olması patojen olmayı teşvik eder. [Yarwood and Schlievert (2003)’den uarlanmıştır, Çizim: M. K. AVCI] 17 Murat Kemal AVCI_İTÜ_MOBGAM www. quorumsensing. net
QUORUM SENSING CROSS TALK 02. 12. 2009 Türler arası Cinsler arası Prokaryot-Ökaryot Ör: S. epidermdis ve S. aureus 18 Murat Kemal AVCI_İTÜ_MOBGAM www. quorumsensing. net
UYGULAMA ALANLARı 02. 12. 2009 Tıp Yapay Kalp kapakçıkları, implent materyaller Veterinerlik Mastitis. . Ziraat / Botanik Bitkisel hastalıklar. . . Biyoteknoloji Malzeme Mühendisliği Biyo-uyumlu materyaller / ürünler Medikal Teknolojileri Moleküler Biyoloji Biyoremediasyon Atık arıtımı. . . Fermentasyon Endüstriyel Mikrobiyoloji Murat Kemal AVCI_İTÜ_MOBGAM 19 www. quorumsensing. net
TARTıŞMA VE ÖNERILER 02. 12. 2009 . . . ? ? √√√√√√ 20 Murat Kemal AVCI_İTÜ_MOBGAM www. quorumsensing. net
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02. 12. 2009 Teşekkürler. . . 27
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