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--- home:publications:marshall_metagenomics_2007 [12.21.2008] – paulalbert
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+~~NOTOC~~
+====== Poster - Bacterial capnine blocks transcription of human antimicrobial peptides ======
+**Type:** Poster presentation\\
+**Presented by:**  Trevor Marshall, PhD\\
+**Conference:**  [[https://metagenomics.calit2.net/2007/index.php|Third International Conference on Metagenomics]]\\
+**Location:**  University of California, San Diego\\
+**Date:**  July 11-13, 2007\\
+**Additional content:** [[https://autoimmunityresearch.org/transcripts/metagenomics2007.pdf|poster]] (includes a number of Wirostko photographs); [[https://precedings.nature.com/documents/164/version/1|post at Nature Precedings]]\\
+===== Abstract =====
+The US CDC believes that 65% of all infections in
+developed countries may be caused by pathogens in
+biofilms. Electron Microscopy has shown that these
+bacterial communities can evade phagocytosis, and persist
+in the cytoplasm of monocytes, macrophages, lymphocytes
+and neutrophils. Three decades ago, Wirostko, et al, found
+such intraphagocytic communities in Crohn’s disease,
+Juvenile Rheumatoid Arthritis and Sarcoidosis(({{pmid>long:8140710}})).
+However, the mechanism(s) by which such persistent
+bacteria could evade the immune system have remained
+elusive. Recently, 16S RNA from species of gliding bacteria
+never thought to be able to survive in-vivo, have been
+found in surgically removed biofilms.(({{pmid>long:17501992}})) This study set
+out to identify whether the genomes of these gliding
+bacteria might yield insight into mechanisms by which
+such persistent pathogens could evade phagocytosis.
+==== Methods ====
+A single Type 1 Nuclear Receptor, the VDR
+(commonly known as the ‘Vitamin D Receptor’), is
+responsible for transcription of LL-37, the human
+Cathelicidin antimicrobial peptide, as well as the beta
+Defensin anti-microbial peptides defB2/defB4(({{pmid>long:16002434}})). Disabling
+transcription by the VDR would allow a pathogen to persist
+inside phagocytes without threat from these anti-microbial
+peptides. Static molecular modeling (primarily using
+AutoDock) was used to screen a number of proteins and
+peptides known to be produced by the genomes of the
+gliding bacteria.
+==== Results ====
+A candidate bacterial sulfonolipid, Capnine, was
+identified to have a nanomolar Ki for the ligand binding
+pocket (LBP) of the VDR. Molecular Dynamics simulation of
+the human VDR in complex with Capnine confirmed that
+this substance is indeed stable in the VDR LBP, and that its
+action is that of a strong transcriptional antagonist.
+==== Conclusion ====
+Medical Metagenomics has demonstrated the
+ability to deliver important results in silico, potentially
+underpinning an infectious pathogenesis for idiopathicnic
+illness.((Waterhouse JC, Marshall TG, Fenter B, Mangin M, Blaney G:
+High levels of active 1,25-dihydroxyvitamin D despite low
+levels of the 25-hydroxyvitamin D precursor - Implications of
+dysregulated vitamin D for diagnosis and treatment of Chronic
+Disease. In Vitamin D: New Research. Volume 1. Edited by:
+Stoltz VD. New York: Nova Science Publishers; 2006.
+ISBN: 1-60021-000-7))((Marshall TG: VDR Nuclear Receptor Competence is the Key
+to Recovery from Chronic Inflammatory and Autoimmune
+Disease. Abstract presentation, DMM2006, Karolinska
+Institute, May 2006. Copy available from URL
+https://autoimmunityresearch.org/karolinska-handout.pdf))
+{{tag>posters Trevor_Marshall_PhD Metagenomics capnine antimicrobial_peptides 2007}}
+===== References =====