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+ | ~~NOTOC~~ | ||
+ | ====== Poster - Bacterial capnine blocks transcription of human antimicrobial peptides ====== | ||
+ | |||
+ | **Type:** Poster presentation\\ | ||
+ | **Presented by:** Trevor Marshall, PhD\\ | ||
+ | **Conference:** [[http://metagenomics.calit2.net/2007/index.php|Third International Conference on Metagenomics]]\\ | ||
+ | **Location:** University of California, San Diego\\ | ||
+ | **Date:** July 11-13, 2007\\ | ||
+ | **Additional content:** [[http://autoimmunityresearch.org/transcripts/metagenomics2007.pdf|poster]] (includes a number of Wirostko photographs); [[http://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(({{pubmed>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.(({{pubmed>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(({{pubmed>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 | ||
+ | http://autoimmunityresearch.org/karolinska-handout.pdf)) | ||
+ | |||
+ | {{tag>posters Trevor_Marshall_PhD Metagenomics capnine antimicrobial_peptides 2007}} | ||
+ | |||
+ | ===== References ===== |
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