ArcAB双组分系统与放线菌聚集菌对超氧化物和过氧化氢的敏感性有关。

IF 3.1 2区 生物学 Q2 MICROBIOLOGY
mSphere Pub Date : 2025-05-27 Epub Date: 2025-04-16 DOI:10.1128/msphere.00019-25
Mohammad Farid Ratman, Yuichi Oogai, Airi Matsumoto, Masanobu Nakata
{"title":"ArcAB双组分系统与放线菌聚集菌对超氧化物和过氧化氢的敏感性有关。","authors":"Mohammad Farid Ratman, Yuichi Oogai, Airi Matsumoto, Masanobu Nakata","doi":"10.1128/msphere.00019-25","DOIUrl":null,"url":null,"abstract":"<p><p><i>Aggregatibacter actinomycetemcomitans</i> 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 <i>A. actinomycetemcomitans</i> remains unclear. In this study, we found that the expression of <i>sod</i>, which encodes superoxide dismutase, was increased in the inactivated mutant of <i>arcA</i>, which encodes a response regulator. The mutant exhibited reduced susceptibility to superoxide and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). Additionally, this strain showed reduced susceptibility to H<sub>2</sub>O<sub>2</sub> from <i>Streptococcus sanguinis</i> and increased survival in macrophages. Since ArcB is the cognate histidine kinase of ArcA, the inactivated mutant of <i>arcB</i> was analyzed for its phenotypes. The <i>arcB</i> mutant exhibited reduced susceptibility to superoxide and H<sub>2</sub>O<sub>2</sub>. Compared to wild type, the phosphorylation level of ArcA in the <i>arcB</i> mutant was decreased. These results suggest that the ArcA response regulator receives phosphate groups from ArcB histidine kinase and negatively regulates the expression of <i>sod</i>, thereby affecting bacterial survival in response to ROS produced by oral commensals and host immune cells.IMPORTANCE<i>Aggregatibacter actinomycetemcomitans</i> 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 <i>A. actinomycetemcomitans</i>, 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.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0001925"},"PeriodicalIF":3.1000,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108069/pdf/","citationCount":"0","resultStr":"{\"title\":\"The ArcAB two-component system is associated with the susceptibility of <i>Aggregatibacter actinomycetemcomitans</i> to superoxide and hydrogen peroxide.\",\"authors\":\"Mohammad Farid Ratman, Yuichi Oogai, Airi Matsumoto, Masanobu Nakata\",\"doi\":\"10.1128/msphere.00019-25\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Aggregatibacter actinomycetemcomitans</i> 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 <i>A. actinomycetemcomitans</i> remains unclear. In this study, we found that the expression of <i>sod</i>, which encodes superoxide dismutase, was increased in the inactivated mutant of <i>arcA</i>, which encodes a response regulator. The mutant exhibited reduced susceptibility to superoxide and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). Additionally, this strain showed reduced susceptibility to H<sub>2</sub>O<sub>2</sub> from <i>Streptococcus sanguinis</i> and increased survival in macrophages. Since ArcB is the cognate histidine kinase of ArcA, the inactivated mutant of <i>arcB</i> was analyzed for its phenotypes. The <i>arcB</i> mutant exhibited reduced susceptibility to superoxide and H<sub>2</sub>O<sub>2</sub>. Compared to wild type, the phosphorylation level of ArcA in the <i>arcB</i> mutant was decreased. These results suggest that the ArcA response regulator receives phosphate groups from ArcB histidine kinase and negatively regulates the expression of <i>sod</i>, thereby affecting bacterial survival in response to ROS produced by oral commensals and host immune cells.IMPORTANCE<i>Aggregatibacter actinomycetemcomitans</i> 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 <i>A. actinomycetemcomitans</i>, 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.</p>\",\"PeriodicalId\":19052,\"journal\":{\"name\":\"mSphere\",\"volume\":\" \",\"pages\":\"e0001925\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108069/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"mSphere\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1128/msphere.00019-25\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"mSphere","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1128/msphere.00019-25","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/16 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

放线菌聚集菌是革兰氏阴性兼性厌氧菌,与牙周病有关。这种细菌暴露于环境压力下,如渗透压、温度变化、pH值变化和抗微生物物质,包括人类口腔中的活性氧(ROS)。细菌双组分系统ArcAB调节基因表达以响应环境变化,主要是通过在几种属于γ-变形细菌的病原体中感知氧压力。它还提供对活性氧胁迫的适应;然而,其在放线菌中的作用尚不清楚。在这项研究中,我们发现编码超氧化物歧化酶的sod在编码应答调节因子的arcA失活突变体中表达增加。突变体对超氧化物和过氧化氢(H2O2)的敏感性降低。此外,该菌株对血链球菌H2O2的敏感性降低,在巨噬细胞中的存活率提高。由于ArcB是ArcA的同源组氨酸激酶,我们对ArcB灭活突变体进行表型分析。arcB突变体对超氧化物和H2O2的敏感性降低。与野生型相比,ArcA的磷酸化水平在arcB突变体中降低。这些结果表明,ArcA应答调节因子接受来自arb组氨酸激酶的磷酸基团,负调控sod的表达,从而影响细菌对口服共生体和宿主免疫细胞产生的ROS的存活。放线菌是一种口腔病原体,已知是一种高毒性的牙周病原体,表现出很强的牙周组织粘附性和毒素产生,导致侵袭性牙周炎。这种细菌不仅与口腔感染有关,而且与全身感染有关,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具有重要意义。细菌双组分系统(TCSs)已被研究为阐明细菌在宿主中的适应性和致病性的有吸引力的目标。本研究鉴定了a .放线菌comitans (ArcAB)的TCS,该TCS与宿主细胞或口腔共生体产生的ROS易感性有关。我们的研究结果为了解细菌对氧化应激的适应机制提供了见解,这对于了解牙周病原体的生存策略至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The ArcAB two-component system is associated with the susceptibility of Aggregatibacter actinomycetemcomitans to superoxide and hydrogen peroxide.

Aggregatibacter actinomycetemcomitans 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 A. actinomycetemcomitans remains unclear. In this study, we found that the expression of sod, which encodes superoxide dismutase, was increased in the inactivated mutant of arcA, which encodes a response regulator. The mutant exhibited reduced susceptibility to superoxide and hydrogen peroxide (H2O2). Additionally, this strain showed reduced susceptibility to H2O2 from Streptococcus sanguinis and increased survival in macrophages. Since ArcB is the cognate histidine kinase of ArcA, the inactivated mutant of arcB was analyzed for its phenotypes. The arcB mutant exhibited reduced susceptibility to superoxide and H2O2. Compared to wild type, the phosphorylation level of ArcA in the arcB mutant was decreased. These results suggest that the ArcA response regulator receives phosphate groups from ArcB histidine kinase and negatively regulates the expression of sod, thereby affecting bacterial survival in response to ROS produced by oral commensals and host immune cells.IMPORTANCEAggregatibacter actinomycetemcomitans 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 A. actinomycetemcomitans, 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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
mSphere
mSphere Immunology and Microbiology-Microbiology
CiteScore
8.50
自引率
2.10%
发文量
192
审稿时长
11 weeks
期刊介绍: mSphere™ is a multi-disciplinary open-access journal that will focus on rapid publication of fundamental contributions to our understanding of microbiology. Its scope will reflect the immense range of fields within the microbial sciences, creating new opportunities for researchers to share findings that are transforming our understanding of human health and disease, ecosystems, neuroscience, agriculture, energy production, climate change, evolution, biogeochemical cycling, and food and drug production. Submissions will be encouraged of all high-quality work that makes fundamental contributions to our understanding of microbiology. mSphere™ will provide streamlined decisions, while carrying on ASM''s tradition for rigorous peer review.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信