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- Role of bacterial γ-glutamyltranspeptidase as a novel virulence factor in bone-resorbing pathogenesis
- Jinmoon Kim , Sungil Jang , Aeryun Kim , Hanfu Su , Niluka Gunawardhana , Yeong-Eui Jeon , Eun Jung Bak , Ji-Hye Kim , Jeong-Heon Cha
- J. Microbiol. 2016;54(5):396-402. Published online April 20, 2016
- DOI: https://doi.org/10.1007/s12275-016-6137-1
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Abstract
- Mammalian γ-glutamyltranspeptidase (GGT) has been identified as a bone-resorbing factor. Since GGT of Bacillus subtilis exhibits similarity in their primary structure and enzymatic characteristics with mammalian GGTs, the bone-resorbing activity of bacterial GGT was examined in this study. Osteoclastogenesis was performed in a co-culture system of mouse calvaria-derived osteoblasts and bone marrow cells. A conditioned medium from GGT-overproducing B. subtilis culture showed significantly higher activity of osteoclast formation than a conditioned medium from wild-type B. subtilis culture. Recombinant GGT (rGGT) of wild-type B. subtilis and an enzymatic activity-defected 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 bone-resorbing 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 kappa-B ligand (RANKL) and cyclooxygenase-2 (COX-2), 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 bone-resorbing virulence factor via RANKL-dependent 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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- Bacterial Gamma-Glutamyl Transpeptidase, an Emerging Biocatalyst: Insights Into Structure–Function Relationship and Its Biotechnological Applications
Meenu Saini, Amuliya Kashyap, Shruti Bindal, Kuldeep Saini, Rani Gupta
Frontiers in Microbiology.2021;[Epub] CrossRef - Quantitative analysis of γ-glutamylpeptides by liquid chromatography-mass spectrometry and application for γ-glutamyltransferase assays
Sho Kobayashi, Yoshinori Tokairin, Takeru Miyakoshi, Takuya Saito, Keita Nagaoka, Yoshitaka Ikeda, Junichi Fujii, Hiroyuki Konno
Analytical Biochemistry.2019; 578: 13. CrossRef - Isolation of γ-Glutamyl-Transferase Rich-Bacteria from Mouse Gut by a Near-Infrared Fluorescent Probe with Large Stokes Shift
Tao Liu, Qiu-Long Yan, Lei Feng, Xiao-Chi Ma, Xiang-Ge Tian, Zhen-Long Yu, Jing Ning, Xiao-Kui Huo, Cheng-Peng Sun, Chao Wang, Jing-Nan Cui
Analytical Chemistry.2018; 90(16): 9921. CrossRef - Heterologous expression and enzymatic characterization of γ-glutamyltranspeptidase from Bacillus amyloliquefaciens
Jung-Min Lee, Jaejung Lee, Gyeong-Hwa Nam, Byung-Sam Son, Myoung-Uoon Jang, So-Won Lee, Byung-Serk Hurh, Tae-Jip Kim
Journal of Microbiology.2017; 55(2): 147. CrossRef - Scientific Opinion on the update of the list of QPS‐recommended biological agents intentionally added to food or feed as notified to EFSA†
Antonia Ricci, Ana Allende, Declan Bolton, Marianne Chemaly, Robert Davies, Rosina Girones, Lieve Herman, Konstantinos Koutsoumanis, Roland Lindqvist, Birgit Nørrung, Lucy Robertson, Giuseppe Ru, Moez Sanaa, Marion Simmons, Panagiotis Skandamis, Emma Snar
EFSA Journal.2017;[Epub] CrossRef
- Bacterial Gamma-Glutamyl Transpeptidase, an Emerging Biocatalyst: Insights Into Structure–Function Relationship and Its Biotechnological Applications
- Mouse Strain-Dependent Osteoclastogenesis in Response to Lipopolysaccharide
- Ho Gil Choi , Jin Moon Kim , Bong-Ju Kim , Yun-Jung Yoo , Jeong-Heon Cha
- J. Microbiol. 2007;45(6):566-571.
- DOI: https://doi.org/2607 [pii]
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Abstract
- Bacterial lipopolysaccharide (LPS) is a potent stimulator of bone resorption in periodontitis. Co-culture systems of mouse calvaria-derived osteoblasts and bone marrow-derived preosteoclasts were used as an in vitro osteoclast differentiation. This study revealed that co-cultures using ddY or ICR mouse strain responded differently to LPS while responded equally to 1α,25(OH)2D3. Thus, the different response to LPS indicates dissimilarity of two mouse stains in their capacity for generating osteoclasts while the two mouse strains share the similarity in response to 1α,25(OH)2D3. To identify which cells between osteoblasts and preosteoclasts in the co-culture are responsible for the dissimilarity, the reciprocal co-cultures were performed between ddY and ICR mouse strains. The treatment of 1,25(OH)2D3 to ddY/ICR (osteoblasts from ddY/preosteoclasts from ICR) and ICR/ddY reciprocal co-cultures also showed the similarity. In case of LPS treatment, the results of ddY/ICR were similar to ddY/ddY and the results of the other reciprocal co-culture, ICR/ddY combination, were consistent with those of ICR/ICR. It suggests that the dissimilarity between the two mouse strains may resident in osteoblasts but not in preosteoclasts. Therefore, the osteoblast is responsible for mouse strain-dependent osteoclastogenesis in response to LPS. Although mouse models will continue to provide insights into molecular mechanisms of osteoclastogenesis, caution should be exercised when using different mouse strains, especially ddY and ICR strains as models for osteoclast differentiation.
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