Detailseite
Projekt
The role of the Chlamydia pneumoniae protein Pmp21 during infection
Antragsteller
Professor Dr. Johannes H. Hegemann
Fachliche Zuordnung
Immunologie
Förderung
Förderung von 2007 bis 2015
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 21644054
Chlamydiae are significant human pathogens. Chlamydia trachomatis is responsible for a spectrum of acute ocular and genital tract infections and for chronic diseases that lead to blindness and tubal-factor infertility, such as trachoma and salpingitis, respectively (1). Chlamydia pneumoniae is an important respiratory pathogen associated with 5 to 10 % of community-acquired cases of pneumonia worldwide and a seroprevalence of up to 70%. (2). Chlamydiae are characterized by a unique biphasic developmental cycle that modulates between an extracellular infectious elementary body (EB) and an intracellular noninfectious reticulate body (RB) which replicates within an inclusion in the eukaryotic cell. Despite its relevance very little is known about the molecular mechanism of a chlamydial infection (3, 4). In our RU project we focus on the initial and most important step of the C. pneumoniae infection cycle: the characterization of the molecular interaction of the pathogen with its human host cell during adhesion of the infectious bacteria to and their subsequent internalization by the human cell. Using a recently developed yeast surface display system we identified the polymorphic membrane protein Pmp21 as a second C. pneumoniae adhesin. Work of the last 2 years has revealed that Pmp21 is a bona fide chlamydia adhesin. A detailed deletion and mutational analysis identified 2 short, repetitive amino acid motifs as being necessary for Pmp21 binding to human cells. Pmp21 is relevant for the infection, as pre-incubation of eukaryotic cells with antibody or recombinant protein dose-dependently reduced infection. Pmp21 belongs to a family of 21 proteins and our recent data show that Pmp6 and Pmp20, two other family members, are also important for adhesion and establishment of infection suggesting that possibly the entire Pmp protein family might be involved in this aspect of the C. pneumoniae infection. Biochemical approaches as well as a yeast 2 hybrid screen identified potential human Pmp21-interacting proteins. In future we plan to pursue our efforts to characterize the human receptor. Further characterization of the 2 new adhesins will deepen our understanding of the role of the Pmp protein family in bacterial attachment to and potentially uptake by the human cell. In vivo Pmp21 is found in processed forms and our first data indicate that these forms interact with each other as well as with other Pmp family members. Thus, our goal is to decipher the potential interaction network of Pmp21 to define its role in the infection process. Finally we also want to study the potential role of the Pmp protein family in antigenic variation which would be relevant for immune escape.
DFG-Verfahren
Forschungsgruppen
