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Role of bacterial γ-glutamyltranspeptidase as a novel virulence factor in bone-resorbing pathogenesis

  • Microbial Pathogenesis and Host-Microbe Interaction
  • Published:
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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 bone-resorbing 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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Author notes

  1. Jinmoon Kim

    Present address: ATGen Ltd, Bundang-gu, Seongnam-si, 13488, Gyeonggi-do, Republic of Korea

  2. Niluka Gunawardhana

    Present address: OMFS Unit, District General Hospital, Nuwara Eliya, Sri Lanka

Authors and Affiliations

  1. Department of Oral Biology, Oral Science Research Center, BK21 Plus Project, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea

    Jinmoon Kim, Sungil Jang, Aeryun Kim, Hanfu Su, Niluka Gunawardhana, Yeong-Eui Jeon, Eun Jung Bak & Jeong-Heon Cha

  2. Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, 03722, Republic of Korea

    Sungil Jang, Aeryun Kim, Hanfu Su & Jeong-Heon Cha

  3. Department of Dental Hygiene, Jeonju Kijeon College, Jeonju, 560-701, Republic of Korea

    Ji-Hye Kim

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  1. Jinmoon Kim
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Correspondence to Ji-Hye Kim or Jeong-Heon Cha.

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Kim, J., Jang, S., Kim, A. et al. Role of bacterial γ-glutamyltranspeptidase as a novel virulence factor in bone-resorbing pathogenesis. J Microbiol. 54, 396–402 (2016). https://doi.org/10.1007/s12275-016-6137-1

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  • DOI: https://doi.org/10.1007/s12275-016-6137-1

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