The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection

Frontiers in Cellular and Infection Microbiology, Год журнала: 2025, Номер 14

Опубликована: Янв. 27, 2025

Attachment and uptake into host cells are pivotal steps in the life cycle of Chlamydiaceae , a family obligate intracellular pathogens. Chlamydia trachomatis (Ctr) possesses nine polymorphic membrane proteins (Pmps), which have been shown to be crucial for adhesion internalization. However, host-cell molecules involved so far remained unknown. Here, we show that fragment Ctr PmpD, forms high-molecular-weight oligomers solution adheres epithelial cells, also binds secreted clusterin (sCLU), chaperone-like protein is extracellular space by cell, part chaperone- receptor-mediated degradation (CRED) pathway. Using vitro assays, demonstrate sCLU interacts directly with soluble rPmpD. In infection experiments, depletion from culture medium leads significant decrease infection. Thus, first interaction partner identified Pmp case has vital component establishment bacterial

Язык: Английский

Immunization Against Chlamydia trachomatis Polymorphic Membrane Protein D Tetrapeptide Motifs Limits Early Female Reproductive Tract Infection in a Mouse Model

Vaccines, Год журнала: 2025, Номер 13(3), С. 234 - 234

Опубликована: Фев. 25, 2025

Background/Objectives: Chlamydia trachomatis (Ct) is a common pathogen causing urogenital, anal, oral, and ocular infections. Although extensive vaccine efforts have been underway for decades, there no licensed available to prevent human Ct infection. Polymorphic membrane protein D (PmpD) highly conserved present on the surface of elementary bodies, suggesting an important role biology. Repetitive tetrapeptide motifs GGA(I,L,V) FxxN are across Pmps adhesion in related pneumoniae Pmp21. Methods: Using bioinformatics approaches, we identified amino acids 270 294 PmpD that included two motif as targets. Synthetic peptides corresponding these regions were chemically conjugated separately via carboxy (C)- or (N)-terminus (FxxN 1.1 1.2) Qβ virus-like particles (VLPs) tested immunogenicity protective capacity mice. Results: Female mice immunized three times with mixture Qβ-FxxN 1.2 vaccines without exogenous adjuvant elicited geometric-mean endpoint dilution titers near 104. Further, showed decreased infection at early time points when challenged vaginally luciferase-expressing muridarum over 9 days faster undetectable compared controls. Immunization individual (Qβ-FxxN did not show same degree reduction. Conclusions: Vaccination against novel promising approach limiting initial warrants further investigation characterize mechanism protection.

Язык: Английский

Pathogenicity and virulence of chlamydia trachomatis : Insights into host interactions, immune evasion, and intracellular survival

Virulence, Год журнала: 2025, Номер unknown

Опубликована: Май 12, 2025

Chlamydia trachomatis is an obligate intracellular pathogen and the leading cause of bacterial sexually transmitted infections infectious blindness worldwide. All species share a unique biphasic developmental cycle, alternating between elementary bodies (EBs) replicative reticulate (RBs). The pathogenesis C. driven by sophisticated arsenal adhesins, conventional type III secretion system effector proteins, inclusion membrane proteins that subvert host cellular processes to establish infection promote survival. In this review, we highlight molecular mechanisms underlying infection, focusing on key stages its including adhesion, invasion, replication, egress. We delve into interactions with cytoskeletal structures, immune signalling pathways, trafficking systems, as well strategies for evasion persistence. Understanding these offers critical insights identifies promising avenues therapeutic vaccine development.

Язык: Английский