Streptococcal cell surface proteins : structure and gene characterisation

Viatcheslav Katerov

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Streptococcus pyogenes (group A streptococci, GAS) is a potent human pathogen known to express a number of cell surface associated virulence factors. It is an established fact that these different surface proteins play an important role during infection. Thus, M family proteins interact with host immune system components allowing streptococci to evade phagocytosis. Another important group of bacterial surface proteins, fibronectin-binding proteins, appear to mediate adherence and invasion of bacteria into host cells. The major part of the virulence regulon mga of GAS, M type 15, was sequenced and deduced proteins compared with known M family proteins. It was thereby revealed that M15 is an OF-positive serotype with low expression of the serum opacity factor (SOF); this was confirmed using a refined method for extraction of SOF from streptococcal cells. Recombinant Emm15 protein was characterized in binding tests with several host proteins and found uniquely to interact with the human subclasses IgG1 and 3. In the present investigation it was found that the fibronectin-binding protein F also specifically binds fibrinogen; the binding of fibronectin and fibrinogen was also shown to occur by different parts of the protein F molecule. Furthermore, the prtF genes of 12 GAS strains representing various serotypes were sequenced from the N-terminus and aligned revealing a more limited variability of protein F compared to streptococcal Emm protein; various recombination events following horizontal gene transfer, as well as point mutations were deduced. Another fibronectin binding protein, SOF of serotype M63, was also cloned. Its overall structure and gene sequence showed high agreement with a known SOF, from type M22, as well as FnBA, a fibronectin-binding protein from Streptococcus dysgalactiae. The presence of OF activity of FnBA was verified experimentally. Based on their archtecture, in particular contiguous regions with either high or low homology between SOF22, SOF63 and FnBA, occupying the major, enzymatically active part of the respective proteins, as well as closely related C-terminal, fibronectin-binding repeats, these proteins could be classified as representatives of a distinct group of bifunctional proteins occurring in groups A and C streptococci.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Division of Medical Microbiology
Supervisors/Advisors
  • [unknown], [unknown], Supervisor, External person
Award date2000 Sep 26
Publication statusPublished - 2000

Bibliographical note

Defence details

Date: 2000-09-26
Time: 09:15
Place: Rune Grubb salen, BMC, Sölvegatan 19

External reviewer(s)

Name: Podbielski, Andreas
Title: Prof
Affiliation: Department of Medical Microbiology and Hygiene, University Hospital, Rostock, Germany

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Subject classification (UKÄ)

  • Microbiology in the medical area

Keywords

  • Mikrobiologi
  • mycology
  • virology
  • bacteriology
  • virologi
  • mykologi
  • Microbiology
  • bakteriologi

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