Department of Basic and Clinical Sciences, Albany College of Pharmacy and Health Sciencesgrid.413555.3, Albany, New York, USA.
Department of Pathology, Microbiology, and Immunology, New York Medical Collegegrid.260917.b, Valhalla, New York, USA.
J Bacteriol. 2022 May 17;204(5):e0008222. doi: 10.1128/jb.00082-22. Epub 2022 Apr 27.
Francisella tularensis is an intracellular, Gram-negative bacterium known for causing a disease known as tularemia in the Northern Hemisphere. F. tularensis is classified as a category A select agent by the CDC based on its possible use as a bioterror agent. F. tularensis overcomes oxidative stress encountered during its growth in the environment or host macrophages by encoding antioxidant enzymes such as superoxide dismutases, catalase, and alkylhydroperoxy reductase. These antioxidant enzymes are regulated by the oxidative stress response regulator, OxyR. In addition to these antioxidant enzymes, F. tularensis also encodes two thioredoxins, TrxA1 () and TrxA2 (); however, their role in the oxidative stress response of F. tularensis is not known. This study investigated the role of thioredoxins of F. tularensis in the oxidative stress response and intracellular survival. Our results demonstrate that TrxA1 but not TrxA2 plays a major role in the oxidative stress response of F. tularensis. Most importantly, this study elucidates a novel mechanism through which the TrxA1 of F. tularensis controls the oxidative stress response by regulating the expression of the master regulator, . Further, TrxA1 is required for the intramacrophage survival and growth of Overall, this study describes a novel role of thioredoxin, TrxA1, in regulating the oxidative stress response of F. tularensis. The role of thioredoxins in the oxidative stress response of F. tularensis is not known. This study demonstrates that of the two thioredoxins, TrxA1 is vital to counter the oxidative stress in F. tularensis live vaccine strain (LVS). Furthermore, this study shows differences in the well-studied thioredoxins of Escherichia coli. First, the expression of TrxA1 of F. tularensis is independent of the oxidative stress response regulator, OxyR. Second and most importantly, TrxA1 regulates the expression of and, therefore, the OxyR-dependent oxidative stress response of F. tularensis. Overall, this study reports a novel regulatory role of TrxA1 of F. tularensis in the oxidative stress response.
弗朗西斯氏土拉菌是一种细胞内革兰氏阴性细菌，已知会在北半球引起土拉菌病。根据其可能被用作生物恐怖制剂的用途，疾病预防控制中心将 F. tularensis 列为 A 类选择剂。F. tularensis 通过编码抗氧化酶（如超氧化物歧化酶、过氧化氢酶和烷烃过氧化物还原酶）来克服其在环境或宿主巨噬细胞中生长时遇到的氧化应激。这些抗氧化酶受氧化应激反应调节剂 OxyR 调节。除了这些抗氧化酶外，F. tularensis 还编码两种硫氧还蛋白，TrxA1 () 和 TrxA2 (); 然而，它们在 F. tularensis 氧化应激反应中的作用尚不清楚。本研究调查了 F. tularensis 硫氧还蛋白在氧化应激反应和细胞内存活中的作用。我们的结果表明，TrxA1 而不是 TrxA2 在 F. tularensis 的氧化应激反应中起主要作用。最重要的是，这项研究阐明了一种新的机制，通过该机制，F. tularensis 的 TrxA1 通过调节主调节剂的表达来控制氧化应激反应。进一步，TrxA1 是 F. tularensis 在内巨噬细胞存活和生长所必需的。总的来说，本研究描述了 F. tularensis 硫氧还蛋白 TrxA1 调节其氧化应激反应的新机制。
F. tularensis 中硫氧还蛋白在氧化应激反应中的作用尚不清楚。本研究表明，在两种硫氧还蛋白中，TrxA1 对于对抗弗氏土拉菌活疫苗株 (LVS) 的氧化应激至关重要。此外，本研究显示了在研究充分的大肠杆菌硫氧还蛋白中存在差异。首先，F. tularensis 的 TrxA1 表达独立于氧化应激反应调节剂 OxyR。其次，也是最重要的是，TrxA1 调节和的表达，因此调节 F. tularensis 的 OxyR 依赖性氧化应激反应。总的来说，本研究报告了 F. tularensis TrxA1 在氧化应激反应中的新的调节作用。
