Bacteria S.aureus and its Wall teichoic acid

Transcription

1 Bacteria S.aureus and its Wall teichoic acid 16.January.2016 Xuehua Li

2 Skin- the Staphylococcal eco system. In 30 40% of the population 2

3 ... and source for invasive infections skin Lung Catheter Wounds,... 3

4 S. aureus is highly versatile Wound-Infections Blood stream-infections Chronic Infections 4

5 Why do certein bacteria cause infections? What can bacteria do when resources get limited? 1. Inhibiting competitors e.g.. S. epidermidis: Frequent producer of bacteriocins 2. Colonizing new habitats E.g.. S. aureus: infects host tissues 5

6 Antibiotics/Bacteriocins are microbial products Antibiotics producer have specific resistence genes E.g.. Antibiotics vancomycin: Produced by soil bacteria (Streptomyceten) Lateral transfer of resistence genes! Vancomycin Streptomyces Resistence genes Enterococcus Staphylococcus 6

7 The Staphylococcus aureus-story 1941 Penicillin 1961 Penicillinase-resistent Penicilline (Methicillin) CH 3 Glycopeptide (Vancomycin) H H H CH 3 H H3 N Cl H HN N H Cl H N N H H N H NH H 2 N NH 2 H H H % resistence by penicillinases 2012 Up to 60% resistance (MRSA) cases of Vancoresistence (VRSA)! 7

8 MRSA-prevalence in Europe

9 MRSA prevalence in Europe Germany 2001: 5-10% Germany 2007: 10-25% EARSS Annual Report

10 How resistence arises and disseminates? Spontaneous mutation Usually only weak resistence Transformation tansfer of naked DNA Conjugation direct transfer between bacterial cells Transduction via bacteriophages 10

11

12 Wall teichoic acids Bacterial Adhesion and colonisation Phage binding Autolysis and division Brown et al, 2013 Antibiotic resistance Immune Interaction

13 Why bacteriophages? 1. Most abundant microorganism 2. Basis for Molecular Biology 3. Bacterial evolution and virulence 4. Application: 1) Phage typing 2) Phage as an antimicrobial agent: phage therapy, plant disease control biocontrol foodborne pathogens 3) Tools for molecular biology

14 Major groups of S.aureus phage Brandis 1984

15 TarS-mediated ß-GlcNAc supposed to be a potent receptor for serogroup G podovirus

16 Podovirus infection ability in different sequence types of S.aureus Many common S.aureus are resistant to podovirus infection

17 The different susceptible pattern of RN4220 mutants to podovirus infection wt M S MS MS/M MS/S K α-glcnac WTA of S.aureus inhibits the susceptability of RN4220 to podovirus infection. β-glcnac WTA are required for podovirus infection.

18 The different susceptible pattern of MRSA strain USA300 mutants to podovirus infection wt M S MS MS/M MS/S K

19 Adsorption assay of podovirus to RN4220 different mutants The resistance or susceptibility between RN4220 wt and mutants to podovirus infection was due to its respective adsorption ability.

20 Tas-mediated ß-GlcNAc is the receptor for podoviridae infection and adsorption K Knock-out tars in PS66 strain abrogates podovirus infection and TarS-complemented PS66 tars mutant restores the susceptibility to podovirus infection. It was confirmed by the adsorption assay.

21 Hybrid strain with tarfijls cluster Species/Strain WTA type Glycosylation Reference S.aureus PS187 GroP GalNAc (a) Winstel, nat commu PS187-H Grop, RboP GalNAc (a), ß-GlcNAc Winstel, nat commu S.Carnosus TM300 GroP Glc, (GalNAc) Winstel, nat commu TM300-H GroP, RboP GalNAc, ß-GlcNAc Winstel, nat commu S.aureus S.carnosus PS187 PS187-H TM300 TM300-H K 44 β-glcnac ribitol phosphate WTA is sufficient for podovirus infection

22 TarM-complemented PS66 strain become resistant to podovirus infection K verexpression of α-glcnac WTA on S.aureus strain inhibits podovirus infection.

23 tars 5SL point mutation was crucial for podovirus infection Staphylococcal complement inhibitor (SCIN) Chemotaxis inhibitory protein (CHIPS) Staphylokinase (SAK) Enterotoxin A (Sea) Enterotoxin P (Sep) ΦSa3/IEC CA-MRSA #50148 #51726 LA-MRSA #55488 #61599 LA-MRSA #61597 LA-MRSA #82086 TarM ψ ψ ψ ψ TarS WT WT 5SL WT DltABCD WT WT WT WT

24 K Complemented with intact tars but not tarm can restore the susceptibilty of ST tars strain to podoviridae infection.

25 tars 5SL point mutation was crucial for podovirus infection K Point mutation in tars of ST398 strain impaired its susceptibility to podovirus infection

26 Summary Tas-mediated ß-GlcNAc is the receptor for podoviridae infection and adsorption and sufficient for podovirus infection. Dominant expression of α-glcnac WTA of S.aureus blocks podiviridae infection and adsorption. tars 5SL point mutation was crucial for serogroup G phages infection.

27 ur current WTA team: Prof. Andreas Peschel Volker Winstel Xuehua Li Petra Kühner David Gerlach The University of Manchester Dr. Guoqing Xia SFB/Transregio 34 Pathophysiologie von Staphylokokken in der Post-Genom Ära