Effects of Ureaplasma parvum infection in the exosome biogenesis‐related proteins in ectocervical epithelial cells

Abstract

Ureaplasma parvum is a mycoplasma commonly associated with female reproductive pathologies, such as preterm birth and infertility. It can survive intracellularly and utilize exosomes to propagate infection and its virulence factors. This study explored the differential protein composition of exosomes derived from normal and U. parvum‐infected cells. We also investigated the impact of U. parvum on exosome biogenesis in ectocervical epithelial cells. Ectocervical epithelial (ECTO) cells were infected with U. parvum, and immunocytochemical staining was performed using U. parvum‐specific marker multiple banded antigen (mba) and exosome marker CD9. NanoLC–MS/MS analysis was conducted to identify differentially expressed proteins in exosomes. Ingenuity Pathway Analysis (IPA) was performed to identify affected canonical pathways and biological functions associated with the protein cargo of exosomes. Western blot analysis of ECTO cells validated the proteomic findings in ECTO cells. U. parvum exhibited colonization of ECTO cells and colocalization with CD9‐positive intraluminal vesicles. Proteomic analysis revealed decreased protein abundance and distinct protein profiles in exosomes derived from U. parvum‐infected ECTO cells. Differentially expressed proteins were associated with clathrin‐mediated endocytosis and various signaling pathways indicative of infection, inflammation, and cell death processes. Additionally, U. parvum infection altered proteins involved in exosome biogenesis. In ECTO cells, U. parvum infection significantly decreased clathrin, ALIX, CD9, and CD63 and significantly increased TSG101, Rab5, Rab35, and UGCG. These findings contribute to our understanding of the infection mechanism and shed light on the importance of exosome‐mediated communication in the pathophysiology of diseases affecting the cervix, such as cervicitis and preterm birth.

Cargo exchange between human and bacterial extracellular vesicles in gestational tissues: a new paradigm in communication and immune development

“…Therefore, the genome, proteome, and metabolome of Lactobacillus-derived EVs can be analyzed to determine if the antimicrobial and anti-inflammatory properties of Lactobacillus spp. such as L. crispatus, which are mainly linked to healthy vaginal microbiota and term delivery [22,[259][260][261] , are exhibited by their EVs independently, and whether such BEVs are bona fide residents of the placenta and fetal membranes. This can be compared to the EV cargo of BV/preterm birth-associated bacterial species such as Gardnerella vaginalis, GBS, and Ureaplasma spp.…”