Ratman Mohammad Farid, Oogai Yuichi, Matsumoto Airi, Nakata Masanobu
Department of Oral Microbiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
mSphere. 2025 May 27;10(5):e0001925. doi: 10.1128/msphere.00019-25. Epub 2025 Apr 16.
is a Gram-negative facultative anaerobe and is associated with periodontal disease. This bacterium is exposed to environmental stresses, such as osmotic pressure, temperature shifts, pH shifts, and antimicrobial substances, including reactive oxygen species (ROS), in the human oral cavity. The bacterial two-component system ArcAB modulates gene expression in response to environmental changes, primarily by sensing oxygen pressure in several pathogens belonging to the γ-proteobacteria. It is also known to provide adaptation to ROS stress; however, its function in remains unclear. In this study, we found that the expression of , which encodes superoxide dismutase, was increased in the inactivated mutant of , which encodes a response regulator. The mutant exhibited reduced susceptibility to superoxide and hydrogen peroxide (HO). Additionally, this strain showed reduced susceptibility to HO from and increased survival in macrophages. Since ArcB is the cognate histidine kinase of ArcA, the inactivated mutant of was analyzed for its phenotypes. The mutant exhibited reduced susceptibility to superoxide and HO. Compared to wild type, the phosphorylation level of ArcA in the mutant was decreased. These results suggest that the ArcA response regulator receives phosphate groups from ArcB histidine kinase and negatively regulates the expression of , thereby affecting bacterial survival in response to ROS produced by oral commensals and host immune cells.IMPORTANCE is an oral pathogen that is known to be a highly virulent periodontal pathogen, showing strong adherence to periodontal tissue and toxin production, which leads to aggressive periodontitis. This bacterium is associated not only with oral infections but also with systemic infections, such as infective endocarditis and brain abscesses. Therefore, elucidating the adaptation mechanisms of this bacterium is important for human health. Bacterial two-component systems (TCSs) have been studied as attractive targets for elucidating bacterial fitness and pathogenicity in the host. This study characterized a TCS in , ArcAB, which is associated with susceptibility to ROS produced by host cells or oral commensals. Our findings provide insights into the bacterial adaptation mechanism against oxidative stress, which is crucial for understanding the survival strategies of the periodontal pathogen.
是一种革兰氏阴性兼性厌氧菌，与牙周疾病有关。这种细菌在人类口腔中会受到环境压力的影响，如渗透压、温度变化、pH值变化以及包括活性氧（ROS）在内的抗菌物质。细菌双组分系统ArcAB主要通过感知γ-变形菌门中几种病原体的氧压力来调节基因表达以应对环境变化。已知它还能使细菌适应ROS应激；然而，其在 中的功能仍不清楚。在本研究中，我们发现编码超氧化物歧化酶的 的表达在编码应答调节因子的 的失活突变体中增加。该突变体对超氧化物和过氧化氢（HO）的敏感性降低。此外，该菌株对来自 的HO敏感性降低，在巨噬细胞中的存活率增加。由于ArcB是ArcA的同源组氨酸激酶，因此对 的失活突变体进行了表型分析。 突变体对超氧化物和HO的敏感性降低。与野生型相比， 突变体中ArcA的磷酸化水平降低。这些结果表明，ArcA应答调节因子从ArcB组氨酸激酶接收磷酸基团并负向调节 的表达，从而影响细菌对口腔共生菌和宿主免疫细胞产生的ROS的应答存活能力。重要性 是一种口腔病原体，已知是一种高毒力的牙周病原体，表现出对牙周组织的强粘附性和毒素产生，这会导致侵袭性牙周炎。这种细菌不仅与口腔感染有关，还与全身感染有关，如感染性心内膜炎和脑脓肿。因此，阐明这种细菌的适应机制对人类健康很重要。细菌双组分系统（TCSs）已被作为阐明细菌在宿主体内适应性和致病性的有吸引力的靶点进行研究。本研究对 中的一个TCS，即ArcAB进行了表征，它与宿主细胞或口腔共生菌产生的ROS敏感性有关。我们的发现为细菌对抗氧化应激的适应机制提供了见解，这对于理解牙周病原体的生存策略至关重要。
