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}
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.
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.