Department of Molecular Microbiology, Washington University School of Medicine in St. Louis , St. Louis, Missouri, USA.
Department of Microbiology and The Center for RNA Biology, The Ohio State University , Columbus, Ohio, USA.
mBio. 2023 Oct 31;14(5):e0141623. doi: 10.1128/mbio.01416-23. Epub 2023 Aug 17.
As deficiencies in tRNA modifications have been linked to human diseases such as cancer and diabetes, much research has focused on the modifications' impacts on translational regulation in eukaryotes. However, the significance of tRNA modifications in bacterial physiology remains largely unexplored. In this paper, we demonstrate that the mG tRNA methyltransferase TrmB is crucial for a top-priority pathogen, , to respond to stressors encountered during infection, including oxidative stress, low pH, and iron deprivation. We show that loss of TrmB dramatically attenuates a murine pulmonary infection. Given the current efforts to use another tRNA methyltransferase, TrmD, as an antimicrobial therapeutic target, we propose that TrmB, and other tRNA methyltransferases, may also be viable options for drug development to combat multidrug-resistant .
由于 tRNA 修饰的缺陷与癌症和糖尿病等人类疾病有关，因此许多研究都集中在修饰对真核生物翻译调控的影响上。然而，tRNA 修饰在细菌生理学中的重要性在很大程度上仍未得到探索。在本文中，我们证明了 mG tRNA 甲基转移酶 TrmB 对于一种首要病原体 至关重要，使其能够应对感染过程中遇到的应激源，包括氧化应激、低 pH 值和缺铁。我们表明，TrmB 的缺失会显著削弱 对小鼠肺部的感染。鉴于目前正在努力将另一种 tRNA 甲基转移酶 TrmD 用作抗菌治疗靶点，我们提出 TrmB 和其他 tRNA 甲基转移酶也可能是开发药物对抗多药耐药 的可行选择。
