Ureaplasma parvum infection alters filamin a dynamics in host cells

Ayman B Allam,Mary B Brown,Sophie Alvarez,Leticia Reyes

doi:10.1186/1471-2334-11-101

Abstract

BackgroundUreaplasmas are among the most common bacteria isolated from the human urogenital tract. Ureaplasmas can produce asymptomatic infections or disease characterized by an exaggerated inflammatory response. Most investigations have focused on elucidating the pathogenic potential of Ureaplasma species, but little attention has been paid to understanding the mechanisms by which these organisms are capable of establishing asymptomatic infection.MethodsWe employed differential proteome profiling of bladder tissues from rats experimentally infected with U. parvum in order to identify host cell processes perturbed by colonization with the microbe. Tissues were grouped into four categories: sham inoculated controls, animals that spontaneously cleared infection, asymptomatic urinary tract infection (UTI), and complicated UTI. One protein that was perturbed by infection (filamin A) was used to further elucidate the mechanism of U. parvum-induced disruption in human benign prostate cells (BPH-1). BPH-1 cells were evaluated by confocal microscopy, immunoblotting and ELISA.ResultsBladder tissue from animals actively colonized with U. parvum displayed significant alterations in actin binding proteins (profilin 1, vinculin, α actinin, and filamin A) that regulate both actin polymerization and cell cytoskeletal function pertaining to focal adhesion formation and signal transduction (Fisher's exact test, P < 0.004; ANOVA, P < 0.02). This phenomenon was independent of clinical profile (asymptomatic vs. complicated UTI). We selected filamin A as a target for additional studies. In the BPH-1 model, we confirmed that U. parvum perturbed the regulation of filamin A. Specifically, infected BPH-1 cells exhibited a significant increase in filamin A phosphorylated at serine2152 (P ≤ 0.01), which correlated with impaired proteolysis of the protein and its normal intracellular distribution.ConclusionFilamin A dynamics were perturbed in both models of infection. Phosphorylation of filamin A occurs in response to various cell signaling cascades that regulate cell motility, differentiation, apoptosis and inflammation. Thus, this phenomenon may be a useful molecular marker for identifying the specific host cell pathways that are perturbed during U. parvum infection.

Highlights

Ureaplasmas are among the most common bacteria isolated from the human urogenital tract
Proteome profiling of F344 rat bladder tissues Two approaches, enrichment analysis and ANOVA, were used to identify proteins that displayed the same response to U. parvum infection regardless of the clinical profile (UTI or Struvite)
Enrichment analysis was performed on protein ratios that were generated by comparing the Negative group to animals that were still actively infected with U. parvum

Summary

Introduction

Ureaplasmas are among the most common bacteria isolated from the human urogenital tract. Ureaplasma parvum and U. urealyticum are among the most common bacteria isolated from the human urogenital tract [1,2,3]. Most infections of the lower urogenital tract appear to be asymptomatic [1] Both species of Ureaplasma are responsible for a variety of diseases such as chorioamnionitis, spontaneous. The animals that remained infected exhibited two distinct clinical profiles of UTI: asymptomatic infection or infection complicated by an exaggerated inflammatory response with bladder stone formation as sequela [11,12,13]. In animals with complicated UTI, U. parvum can be found within the submucosa of the bladder, which may be the driving force behind the persistent and exaggerated inflammatory response

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