An Sun-Jin, Ha Kyung-Won, Jun Hye-Kyoung, Kim Hyun Young, Choi Bong-Kyu
Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Bone Science R&D Center, Osstem Implant Co., Ltd, Seoul, Republic of Korea.
Mol Oral Microbiol. 2023 Feb;38(1):71-81. doi: 10.1111/omi.12380. Epub 2022 Aug 3.
Outer membrane vesicles (OMVs) of bacteria harbor physiologically active molecules, and quorum sensing inhibitors (QSIs) are expected to regulate bacterial virulence. In this study, we analyzed the proinflammatory activity of OMVs of the periodontal pathogen Tannerella forsythia treated with d-arabinose and d-galactose as QSIs, which inhibit the biofilm formation of periodontal pathogens and autoinducer 2 activity. Compared to OMVs of nontreated T. forsythia (TF OMVs), OMVs released from QSI-treated T. forsythia, designated TF ara-OMVs and TF gal-OMVs, showed reduced production of TNF-α, IL-1β, IL-6, and IL-8 in THP-1 monocytes through decreased activation of NF-κB/MAPKs. Using a human NF-κB reporter cell line and bone marrow-derived macrophages from TLR2 mice, TF ara-OMVs and TF gal-OMVs showed less activation of TLR2 than TF OMVs. These results demonstrated that QSIs provide a dual advantage against bacterial infection by inhibiting bacterial biofilm formation and generating OMVs with reduced proinflammatory activity.
细菌的外膜囊泡（OMV）含有生理活性分子，群体感应抑制剂（QSI）有望调节细菌毒力。在本研究中，我们分析了用d -阿拉伯糖和d -半乳糖作为QSI处理的牙周病原体福赛坦氏菌的OMV的促炎活性，这两种物质可抑制牙周病原体的生物膜形成和自诱导物2活性。与未处理的福赛坦氏菌的OMV（TF OMV）相比，经QSI处理的福赛坦氏菌释放的OMV，分别命名为TF ara - OMV和TF gal - OMV，通过降低NF -κB/丝裂原活化蛋白激酶（MAPKs）的激活，使THP - 1单核细胞中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL - 1β）、白细胞介素-6（IL - 6）和白细胞介素-8（IL - 8）的产生减少。使用人NF -κB报告细胞系和来自Toll样受体2（TLR2）小鼠的骨髓来源巨噬细胞，TF ara - OMV和TF gal - OMV对TLR2的激活作用比TF OMV小。这些结果表明，QSI通过抑制细菌生物膜形成和产生促炎活性降低的OMV，为抵抗细菌感染提供了双重优势。
