Polymorphic Membrane Protein 17G of Chlamydia psittaci Mediated the Binding and Invasion of Bacteria to Host Cells by Interacting and Activating EGFR of the Host

Abstract

Chlamydia psittaci (C. psittaci) is an obligate intracellular, gram-negative bacterium, and mainly causes systemic disease in psittacine birds, domestic poultry, and wild fowl. The pathogen is threating to human beings due to closely contacted to employees in poultry industry. The polymorphic membrane proteins (Pmps) enriched in C. psittaci includes six subtypes (A, B/C, D, E/F, G/I and H). Compared to that of the 1 pmpG gene in Chlamydia trachomatis (C. trachomatis), the diverse pmpG gene-coding proteins of C. psittaci remain elusive. In the present study, polymorphic membrane protein 17G (Pmp17G) of C. psittaci mediated adhesion to different host cells. More importantly, expression of Pmp17G in C. trachomatis upregulated infections to host cells. Afterwards, crosstalk between Pmp17G and EGFR was screened and identified by MALDI-MS and Co-IP. Subsequently, EGFR overexpression in CHO-K1 cells and EGFR knockout in HeLa 229 cells were assessed to determine whether Pmp17G directly correlated with EGFR during Chlamydial adhesion. Finally, the EGFR phosphorylation was recognized by Grb2, triggering chlamydial invasion. Based on above evidence, Pmp17G possesses adhesive property that serves as an adhesin and activate intracellular bacterial internalization by recognizing EGFR during C. psittaci infection

A Novel Intranasal Vaccine With PmpGs + MOMP Induces Robust Protections Both in Respiratory Tract and Genital System Post Chlamydia psittaci Infection

“…In a recent report, Pmp17G was associated with host adaptions as an adhesin (17). Furthermore, C. psittacispecific Pmp17G activated Chlamydial invasion in a dependent way by recognizing EGFR, activating Tyr1068 phosphorylation of EGFR, and forming the EGFR-Grb2 complex, contributing to intracellular attachment and internalization during C. psittaci infection (18). In the present study, multiple PmpGs as antigens, Pmp17G, Pmp20G, and Pmp21G were based on our pioneer study.…”

Sequence, Structure, and Epitope Analysis of the Polymorphic Membrane Protein Family in Chlamydia trachomatis

“…A recent Genome-Wide Association study of C. trachomatis serovar G genomes identified polymorphisms in Pmp E, F, and H that are associated with rectal tissue tropism, localized specifically to the side loops in these Pmps (68). Pmps are also known to be directly involved in invasion of host cells by binding to host EGFR in C. pneumoniae (69) and C. psittaci (70). Although the precise mechanisms of these interactions are as yet poorly understood, the proline-rich regions and membrane interaction domains we identified in the side loops may be involved in mediating these interactions.…”

“…A recent Genome-Wide Association study of C. trachomatis serovar G genomes identified polymorphisms in Pmp E, F, and H that are associated with rectal tissue tropism, localized specifically to the side loops in these Pmps (68). Pmps are also known to be directly involved in invasion of host cells by binding to host EGFR in C. pneumoniae (69) and C. psittaci (70).…”

Plasmid-mediated virulence in Chlamydia

“…The surface-exposed, envelope protein OmcB binds glycosaminoglycans on the host cell surface ( Fadel and Eley, 2007 ; Moelleken and Hegemann, 2007 ; Fadel and Eley, 2008 ; Fechtner et al., 2013 ; Liang et al., 2021 ), while the chlamydial major outer membrane protein (MOMP) was shown to potentially bind heparan sulfate receptors on the host cell ( Su et al., 1996 ). Binding of the epithelial growth factor receptor (EGFR) by chlamydial Ctad1( Stallmann and Hegemann, 2016 ) and engagement of β1-integrin by bacterial polymorphic membrane proteins ( Mölleken et al., 2013 ; Luczak et al., 2016 ; Li et al., 2022 ) have also been proposed as adhesion mechanisms. It is likely that multiple mechanisms are combined and utilized by chlamydial EBs for adhesion, given the importance of binding and entry to its intracellular developmental cycle.…”