All subtypes of the Pmp adhesin family are implicated in chlamydial virulence and show species‐specific function

Abstract

The bacterial pathogens Chlamydia trachomatis and C. pneumoniae are obligate intracellular parasites, cause a number of serious diseases, and can infect various cell types in humans. Chlamydial infections are probably initiated by binding of the bacterial outer membrane protein OmcB to host cell glycosaminoglycans (GAGs). Here, we show that all nine members of the polymorphic membrane protein (Pmp) family of C. trachomatis mediate adhesion to human epithelial and endothelial cells. Importantly, exposure of infectious particles to soluble recombinant Pmps blocks subsequent infection, thus implicating an important function of the entire protein family in the infection process. Analogous experiments with pairs of recombinant Pmps or a combination of Pmp and OmcB revealed that all Pmps probably act in an adhesion pathway that is distinct from the OmcB-GAG pathway. Finally, we provide evidence that the Pmps of C. trachomatis and C. pneumoniae exhibit species and tissue specificity. These findings argue for the involvement of C. trachomatis Pmps in the initial phase of infection and suggest that they may interact with a receptor other than the epidermal growth factor receptor recently identified for their counterparts in C. pneumoniae.

The Chlamydia pneumoniae Adhesin Pmp21 Forms Oligomers with Adhesive Properties

“…Chlamydiae enter cells via multiple routes, using mechanisms that are poorly understood (49). In previous studies we identified the Pmp proteins of C. pneumoniae and C. trachomatis as adhesins that are essential for the successful infection of human cells (22,27). Pmps are known to share characteristic features with Type V autotransporters, including proteolytic processing (13,14,16,18,22).…”

“…Adhere to Human Cells-In previous studies, Pmp6, -20, and -21 from C. pneumoniae and all nine Pmps from C. trachomatis serovar E, were characterized as bacterial adhesins that are important for the infection of human epithelial cells (22,27). The motifs GGA(I/L/V) and FXXN are characteristic for Pmps and essential for adhesion (22).…”

“…CD Spectroscopy-Far-UV CD spectra were measured on a JASCO J-815 spectropolarimeter equipped with a 1-mm Supra Adhesion Assays with Protein-coated Latex Beads-Adhesion assays with protein-coated latex beads were performed as described (27). Coating efficiency with 100 g/ml His 6 -tagged proteins was estimated by immunoblotting before use.…”

“…In addition, blocking experiments using recombinant Pmp proteins have provided direct evidence for the critical role of the Pmp proteins in chlamydial pathogenesis (22,27) More recently, the epidermal growth factor receptor (EGFR) was identified as the host receptor for the C. pneumoniae adhesin Pmp21, and binding to EGFR was shown to induce the uptake of the chlamydial EB, thus qualifying Pmp21 as an invasin (28).…”

In Vitro Passage Selects for Chlamydia muridarum with Enhanced Infectivity in Cultured Cells but Attenuated Pathogenicity in Mouse Upper Genital Tract

“…Multiple putative chlamydial factors, such as the major outer membrane protein (MOMP) (10)(11)(12)(13), outer membrane complex (OMC) protein B (OmcB) (14)(15)(16), and the polymorphic membrane proteins (Pmps) (17)(18)(19), and host-derived factors, such as heparin sulfate (16,20), epidermal growth factor receptor (EGFR) (21), estrogen receptor (22), and insulin-like growth factor 2 receptor (23), have been proposed to mediate chlamydial interactions with host cells. However, the precise structural basis of the interactions between an EB and a host cell during chlamydial infection in animals and humans remains ill defined.…”