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Title of Journal: J Microbiol

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Abbravation: Journal of Microbiology

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The Microbiological Society of Korea

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DOI

10.1016/0304-4165(89)90108-6

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1976-3794

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Role of bacterial γglutamyltranspeptidase as a no

Authors: Jinmoon Kim Sungil Jang Aeryun Kim Hanfu Su Niluka Gunawardhana YeongEui Jeon Eun Jung Bak JiHye Kim JeongHeon Cha
Publish Date: 2016/04/20
Volume: 54, Issue: 5, Pages: 396-402
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Abstract

Mammalian γglutamyltranspeptidase GGT has been identified as a boneresorbing factor Since GGT of Bacillus subtilis exhibits similarity in their primary structure and enzymatic characteristics with mammalian GGTs the boneresorbing activity of bacterial GGT was examined in this study Osteoclastogenesis was performed in a coculture system of mouse calvariaderived osteoblasts and bone marrow cells A conditioned medium from GGToverproducing B subtilis culture showed significantly higher activity of osteoclast formation than a conditioned medium from wildtype B subtilis culture Recombinant GGT rGGT of wildtype B subtilis and an enzymatic activitydefected rGGT of B subtilis 2288 mutant were expressed in Escherichia coli and purified using His tag Both purified rGGTs induced similar levels of osteoclastogenesis suggesting that B subtilis GGT possesses virulent boneresorbing activity and its activity is probably independent of its enzymatic activity Furthermore a recombinant protein of B subtilis GGT heavy subunit Bs rGGT/H showed strong activity of osteoclastogenesis while the light subunit failed to show strong activity suggesting that the boneresorbing activity is mainly located at the heavy subunit More importantly the GGT enzymatic activity may not be required for this virulence activity since the light subunit contains the catalytic pocket In addition B subtilis rGGT stimulated mRNA expressions of receptor activator of nuclear factor kappaB ligand RANKL and cyclooxygenase2 COX2 while an osteoprotegerin inhibited the osteoclast formation induced by Bs rGGT/H This is the first demonstration that bacterial GGT itself is sufficient to act as a boneresorbing virulence factor via RANKLdependent pathway Therefore it can be hypothesized that GGT of periodontopathic bacteria may play an important role as a virulence factor in bone destruction

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