title: Ureaplasma parvum infection alters filamin A dynamics in host cells.
abstract: BACKGROUND
  Ureaplasmas 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Bladder 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 serine 2152 (P ≤ 0.01), which correlated with impaired proteolysis of the protein and its normal intracellular distribution.
  
  
  CONCLUSIONS
  Filamin 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.
authors.affiliation: Department of Infectious Disease & Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Ayman B
authors.initials: AB
authors.lastname: Allam
authors.forename: Sophie
authors.initials: S
authors.lastname: Alvarez
authors.forename: Mary B
authors.initials: MB
authors.lastname: Brown
authors.forename: Leticia
authors.initials: L
authors.lastname: Reyes
mesh_terms: D000818:Animals; D002460:Cell Line; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D064448:Filamins; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D014509:Ureaplasma / Q000502:physiology*; D016869:Ureaplasma Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D001743:Urinary Bladder / Q000378:metabolism / Q000382:microbiology; D014552:Urinary Tract Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins