Eckelt Elke, Meißner Thorsten, Meens Jochen, Laarmann Kristin, Nerlich Andreas, Jarek Michael, Weiss Siegfried, Gerlach Gerald-F, Goethe Ralph
Institute for Microbiology, Department of Infectious Diseases, University of Veterinary Medicine Hannover Hannover, Germany.
Genome Analytics, Helmholtz Centre for Infection Research Braunschweig, Germany.
Front Microbiol. 2015 Feb 6;6:16. doi: 10.3389/fmicb.2015.00016. eCollection 2015.
The ferric uptake regulator A (FurA) is known to be involved in iron homeostasis and stress response in many bacteria. In mycobacteria the precise role of FurA is still unclear. In the presented study, we addressed the functional role of FurA in the ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) by construction of a furA deletion strain (MAPΔfurA). RNA deep sequencing revealed that the FurA regulon consists of repressed and activated genes associated to stress response or intracellular survival. Not a single gene related to metal homeostasis was affected by furA deletion. A decisive role of FurA during intracellular survival in macrophages was shown by significantly enhanced survival of MAPΔfurA compared to the wildtype, indicating that a principal task of mycobacterial FurA is oxidative stress response regulation in macrophages. This resistance was not associated with altered survival of mice after long term infection with MAP. Our results demonstrate for the first time, that mycobacterial FurA is not involved in the regulation of iron homeostasis. However, they provide strong evidence that FurA contributes to intracellular survival as an oxidative stress sensing regulator.
已知铁摄取调节因子A（FurA）参与许多细菌的铁稳态和应激反应。在分枝杆菌中，FurA的确切作用仍不清楚。在本研究中，我们通过构建furA缺失菌株（MAPΔfurA）来探讨FurA在反刍动物病原菌副结核分枝杆菌（MAP）中的功能作用。RNA深度测序表明，FurA调控子由与应激反应或细胞内存活相关的受抑制和激活的基因组成。furA缺失未影响任何与金属稳态相关的基因。与野生型相比，MAPΔfurA在巨噬细胞内的存活率显著提高，这表明FurA在巨噬细胞内生存过程中起决定性作用，这表明分枝杆菌FurA的主要任务是调节巨噬细胞中的氧化应激反应。这种抗性与长期感染MAP后小鼠存活率的改变无关。我们的结果首次证明，分枝杆菌FurA不参与铁稳态的调节。然而，它们提供了强有力的证据，表明FurA作为一种氧化应激传感调节因子有助于细胞内存活。
