State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China.
State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi, China; College of Veterinary, National Agricultural University of Kazakhstan, Nur Sultan, Kazakhstan.
Int Immunopharmacol. 2024 Dec 5;142(Pt A):113038. doi: 10.1016/j.intimp.2024.113038. Epub 2024 Sep 13.
Increased glycolytic metabolism recently emerged as an essential process driving host defense against Brucella, but little is known about how this process is regulated during infection. We have identified a critical role for nuclear factor kappa B (NF-κB) transcription factor regulation in glycolytic switching during Brucella infection for the first time. Chromatin immunoprecipitation with next-generation sequencing for NF-κB and DNA Pull-Down revealed two novel NF-κB-binding sites in the enhancer region of the Nitric oxide (NO)production-response regulator gene glucose-6-phosphate dehydrogenase (G6PD), which is important for the switch to glycolysis during a Brucella infection. These findings demonstrate that Brucella drives metabolic reprogramming by inhibiting host oxidative phosphorylation (OXPHOS) and enhancing its glycolysis via the NF-κB-G6PD-NO-pathway. These studies provide a theoretical basis for investigating drugs or vaccines to control Brucella colonization and induction of undulant by manipulating host metabolic patterns.
糖酵解代谢的增加最近被认为是宿主防御布鲁氏菌的一个必要过程，但对于这个过程在感染过程中是如何被调节的，人们知之甚少。我们首次发现，核因子 kappa B（NF-κB）转录因子在布鲁氏菌感染期间的糖酵解转换中起着关键作用。用于 NF-κB 的染色质免疫沉淀和下一代测序以及 DNA 下拉实验揭示了一氧化氮（NO）产生反应调节剂基因葡萄糖-6-磷酸脱氢酶（G6PD）增强子区域中的两个新的 NF-κB 结合位点，该基因对于布鲁氏菌感染期间的糖酵解转换很重要。这些发现表明，布鲁氏菌通过抑制宿主氧化磷酸化（OXPHOS）和通过 NF-κB-G6PD-NO 途径增强其糖酵解来驱动代谢重编程。这些研究为研究通过操纵宿主代谢模式来控制布鲁氏菌定植和诱导波浪热的药物或疫苗提供了理论基础。
