Accession Number:

ADA464803

Title:

The Bacterial Gene IfpA Influences the Potent Induction of Calcitonin Receptor and Osteoclast-Related Genes in Burkholderia Pseudomallei-Induced TRAP-Positive Multinucleated Giant Cells

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD

Report Date:

2006-06-13

Pagination or Media Count:

20.0

Abstract:

Burkholderia pseudomallei is a facultative intracellular pathogen and the causative agent of melioidosis, a spectrum of potentially fatal diseases endemic in Northern Australia and South-East Asia. We demonstrate that B. pseudomallei rapidly modifies infected macrophage-like cells in a manner analagous to osteoclastogenesis. These alterations include multinucleation and the expression by infected cells of mRNA for factors required for osteoclastogenesis the chemokines monocyte chemotactic protein 1 MCP-1, macrophage inflammatory protein 1 gamma MIP-1gamma, regulated on activation normal T cell expressed and secreted RANTES and the transcription factor nuclear factor of activated T-cells cytoplasmic 1 NFATc1. An increase in expression of these factors was also observed after infection with Burkholderia thailandensis. Expression of genes for the osteoclast markers calcitonin receptor CTR, cathepsin K CTSK and tartrate-resistant acid phosphatase TRAP was also increased by B. pseudomallei-infected, but not by B. thailandensis-infected cells. The expression by B. pseudomallei-infected cells of these chemokine and osteoclast marker genes was remarkably similar to cells treated with RANKL, a stimulator of osteoclastogenesis. Analysis of dentine resorption by B. pseudomallei-induced osteoclast-like cells revealed that demineralization may occur but that authentic excavation does not take place under the tested conditions. Furthermore, we identified and characterized lfpA for lactonase family protein A in B. pseudomallei, which shares significant sequence similarity with the eukaryotic protein regucalcin, also known as senescence marker protein-30 SMP-30. LfpA orthologues are widespread in prokaryotes and are well conserved, but are phylogenetically distinct from eukaryotic regucalcin orthologues. We demonstrate that lfpA mRNA expression is

Subject Categories:

  • Biology
  • Anatomy and Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE