成功的病原体必须能够适应宿主施加的多种压力因素。鲍曼不动杆菌由于其对恶劣环境的出色适应能力和多重耐药性激增的速度而成为全球主要的健康威胁。最近的研究已经开始探索tRNA甲基化在细菌应激反应中的重要性，包括对抗生素和氧化应激的适应能力。然而，在鲍曼不动杆菌中尚未研究tRNA甲基转移酶(trms)。生物信息学分析显示，临床鲍曼不动杆菌分离株和实验室菌株之间存在9个推测的依赖于SAM的trms。我们在现代的耐柯利星临床分离株ARC6851中产生了8个trm突变体，并分析了这些突变体的应激反应。其中一个突变体ΔtrmB，在氧化应激下对氧化应激更为敏感，并在低pH下显示出生长缺陷。相应地，ΔtrmB无法在J774A.1巨噬细胞中复制，并在急性肺炎小鼠模型中表现出较低的毒力。随后，我们证明了鲍曼不动杆菌TrmB对m7G tRNA修饰的作用。蛋白质组学分析显示，ARC6851在氧化应激下显著上调了一个依赖于铁载体生物合成和摄取的聚集物，是鲍曼不动杆菌HerA筛定器和吸入混合症。相比之下，ΔtrmB中锭杆菌处的猪链霉素蛋白表达的上调只是轻微的，这影响了其在氧化应激下承受铁限制的能力。qRT-PCR数据表明，TrmB依赖的聚集物调控是转录后的。我们的结果表明，TrmB介导的应激反应对鲍曼不动杆菌的发病机理至关重要，强调了针对trms抵抗多重耐药鲍曼不动杆菌崛起的治疗潜力。该研究表明，鲍曼不动杆菌病原体因缺乏tRNA修饰与癌症和糖尿病等人类疾病有关，因此对tRNA修饰对真核生物的翻译调控的影响进行了很多研究。然而，tRNA修饰对细菌生理过程的重要性仍然大部分没有被探索。本文中，我们展示了m7G tRNA甲基转移酶TrmB对一种优先选择的病原菌鲍曼不动杆菌应对感染中所遇到的应激反应，包括氧化应激、低pH和缺铁的重要性。我们证明，失去TrmB显著削弱了小鼠的肺部感染能力。鉴于目前努力使用另一种tRNA甲基转移酶TrmD作为抗菌治疗靶标，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重耐药鲍曼不动杆菌的可行选项。

Successful pathogens must be able to adapt to a multitude of stressors imposed by their host. Acinetobacter baumannii has emerged as a major global health threat due to its exceptional ability to adapt to hostile environments and skyrocketing rates of multidrug resistance. Recent studies have begun to explore the importance of tRNA methylation in the regulation of bacterial stress responses, including adaptation to antibiotic and oxidative stresses. However, tRNA methyltransferases (trms) have not been investigated in A. baumannii. Bioinformatic analyses revealed nine putative, SAM-dependent trms conserved across clinical A. baumannii isolates and laboratory strains. We generated eight trm mutants in a modern, colistin-resistant clinical isolate, ARC6851, and analyzed the mutants' stress responses. One mutant, ΔtrmB, was vastly more sensitive to oxidative stress and displayed a growth defect at low pH. Accordingly, ΔtrmB was unable to replicate in J774A.1 macrophages and had decreased virulence in an acute pneumonia murine model. Subsequently, we showed that A. baumannii TrmB makes the m7G tRNA modification. A proteomic analysis revealed that ARC6851 significantly upregulates a siderophore biosynthesis and uptake cluster, acinetobactin, under oxidative stress. In contrast, the upregulation of the acinetobactin proteins in ΔtrmB was only modest, which impacted its ability to withstand iron deprivation under oxidative stress. qRT-PCR data showed that TrmB-dependent regulation of acinetobactin is post-transcriptional. Our results indicate that TrmB-mediated stress responses are important for A. baumannii pathogenesis, highlighting the therapeutic potential of targeting trms to combat the rise of multidrug-resistant A. baumannii. IMPORTANCE 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 m7G tRNA methyltransferase TrmB is crucial for a top-priority pathogen, Acinetobacter baumannii, 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 A. baumannii.