PMID- 16987331
OWN - NLM
STAT- MEDLINE
DCOM- 20070710
LR  - 20070207
IS  - 1462-5814 (Print)
IS  - 1462-5814 (Linking)
VI  - 9
IP  - 2
DP  - 2007 Feb
TI  - The bacterial gene lfpA influences the potent induction of calcitonin receptor 
      and osteoclast-related genes in Burkholderia pseudomallei-induced TRAP-positive 
      multinucleated giant cells.
PG  - 514-31
AB  - 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 dramatically increased in association with 
      macrophage-like cells. Mutation of lfpA significantly reduced expression of the 
      tested host genes, relative to the response to wild-type B. pseudomallei. We also 
      show that lfpA is required for optimal virulence in vivo.
FAU - Boddey, Justin A
AU  - Boddey JA
AD  - Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
FAU - Day, Christopher J
AU  - Day CJ
FAU - Flegg, Cameron P
AU  - Flegg CP
FAU - Ulrich, Ricky L
AU  - Ulrich RL
FAU - Stephens, Sebastien R
AU  - Stephens SR
FAU - Beacham, Ifor R
AU  - Beacham IR
FAU - Morrison, Nigel A
AU  - Morrison NA
FAU - Peak, Ian R A
AU  - Peak IR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060920
PL  - India
TA  - Cell Microbiol
JT  - Cellular microbiology
JID - 100883691
RN  - 0 (Receptors, Calcitonin)
RN  - 9007-12-9 (Calcitonin)
SB  - IM
MH  - Animals
MH  - Burkholderia pseudomallei/*genetics/*immunology/physiology
MH  - Calcitonin/metabolism
MH  - Cell Differentiation/physiology
MH  - Cell Line
MH  - Cricetinae
MH  - Disease Models, Animal
MH  - Giant Cells/metabolism/*physiology
MH  - Melioidosis/genetics/*immunology/microbiology
MH  - Mesocricetus
MH  - Osteoclasts/cytology/*metabolism
MH  - Receptors, Calcitonin/*metabolism
EDAT- 2006/09/22 09:00
MHDA- 2007/07/11 09:00
CRDT- 2006/09/22 09:00
PHST- 2006/09/22 09:00 [pubmed]
PHST- 2007/07/11 09:00 [medline]
PHST- 2006/09/22 09:00 [entrez]
AID - CMI807 [pii]
AID - 10.1111/j.1462-5822.2006.00807.x [doi]
PST - ppublish
SO  - Cell Microbiol. 2007 Feb;9(2):514-31. doi: 10.1111/j.1462-5822.2006.00807.x. Epub 
      2006 Sep 20.