Peng Qi, Guo Lu, Dong Yu, Bao Tingrui, Wang Huiyuan, Xu Tao, Zhang Ying, Han Jian
Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, No. 199, Donggang West Rd., Lanzhou 730000, China.
Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai 200040, China.
Antibiotics (Basel). 2022 Nov 25;11(12):1702. doi: 10.3390/antibiotics11121702.
can cause chronic infections which are closely related to persister formation. Purine metabolism is involved in persister formation, and , encoding phosphoribosylglycinamide formyltransferase, is an important gene in the purine metabolism process. In this study, we generated a Δ mutant of the Newman strain and assessed its roles in antibiotic tolerance and virulence. The Δ in the late exponential phase had a significant defect in persistence to antibiotics. Complementation of the Δ restored its tolerance to different antibiotics. PurN significantly affected virulence gene expression, hemolytic ability, and biofilm formation in Moreover, the LD (3.28 × 10 CFU/mL) of the Δ for BALB/c mice was significantly higher than that of the parental strain (2.81 × 10 CFU/mL). Transcriptome analysis revealed that 58 genes that were involved in purine metabolism, alanine, aspartate, glutamate metabolism, and 2-oxocarboxylic acid metabolism, etc., were downregulated, while 24 genes involved in ABC transporter and transferase activity were upregulated in Δ vs. parental strain. Protein-protein interaction network showed that there was a close relationship between PurN and GltB, and SaeRS. The study demonstrated that PurN participates in the formation of the late exponential phase persisters via GltB and regulates its virulence by activating the SaeRS two-component system.
可导致与持留菌形成密切相关的慢性感染。嘌呤代谢参与持留菌形成,且编码磷酸核糖甘氨酰胺甲酰基转移酶的PurN是嘌呤代谢过程中的一个重要基因。在本研究中,我们构建了Newman菌株的ΔPurN突变体,并评估其在抗生素耐受性和毒力方面的作用。处于指数后期的ΔPurN在对抗生素的耐受性方面存在显著缺陷。对ΔPurN进行互补恢复了其对不同抗生素的耐受性。PurN显著影响了金黄色葡萄球菌的毒力基因表达、溶血能力和生物膜形成。此外,ΔPurN对BALB/c小鼠的半数致死剂量(3.28×10⁴CFU/mL)显著高于亲本菌株(2.81×10³CFU/mL)。转录组分析显示,与亲本菌株相比,ΔPurN中58个参与嘌呤代谢、丙氨酸、天冬氨酸、谷氨酸代谢以及2-氧代羧酸代谢等的基因下调,而24个参与ABC转运蛋白和转移酶活性的基因上调。蛋白质-蛋白质相互作用网络表明PurN与GltB以及SaeRS之间存在密切关系。该研究表明,PurN通过GltB参与指数后期持留菌的形成,并通过激活SaeRS双组分系统调节其毒力。