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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Cell. Infect. Microbiol. | doi: 10.3389/fcimb.2019.00398

Group A Streptococcus NAD-glycohydrolase inhibits caveolin 1-mediated internalization into human epithelial cells

  • 1Department of Microbiology, Graduate School of Medicine, Faculty of Medicine, Kyoto University, Japan
  • 2School of Life Dentistry, Nippon Dental University, Japan

Group A Streptococcus (GAS) invades into epithelial cells for persistent infection. GAS has a variety of effector proteins that modulate host systems for their survival in host environments. The main effector proteins of GAS are NAD-glycohydrolase (Nga) and streptolysin O (SLO). Although Nga has NADase activity and shows SLO-dependent cytotoxicity, some clinical isolates harbor NADase-inactive subtypes of Nga, and the function of NADase-inactive Nga is still unclear. In this study, we found that the deletion of nga enhanced the internalization of GAS into HeLa and Ca9-22 cells. Amino acid substitution of Nga R289K/G330D (NADase-inactive) did not enhance GAS invasion, suggesting that Nga may inhibit the internalization of GAS into host cells in a NADase-independent manner. Moreover, double deletion of slo and nga showed similar invasion percentages compared with wild-type GAS, indicating the important role of SLO in the inhibition of GAS invasion by Nga. Furthermore, enhanced internalization of the nga deletion mutant was not observed in Cav1-knockout HeLa cells. Taken together, these findings demonstrated an unrecognized NADase-independent function of Nga as a negative regulator of CAV1-mediated internalization into epithelial cells.

Keywords: Group A Streptoccocus, internalization, CAV1 (caveolin-1), NAD-glycohydrolase, Streptolysin O (SLO)

Received: 15 Feb 2019; Accepted: 06 Nov 2019.

Copyright: © 2019 Toh, Lin, Nakajima, Aikawa, Nozawa and Nakagawa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Ichiro Nakagawa, Department of Microbiology, Graduate School of Medicine, Faculty of Medicine, Kyoto University, Kyoto, 606-8501, Kyōto, Japan, nakagawa.ichiro.7w@kyoto-u.ac.jp