PurN Is Involved in Antibiotic Tolerance and Virulence in <i>Staphylococcus aureus</i>
Qi Peng,
Lu Guo,
Yu Dong,
Tingrui Bao,
Huiyuan Wang,
Tao Xu,
Ying Zhang,
Jian Han
Affiliations
Qi Peng
Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, No. 199, Donggang West Rd., Lanzhou 730000, China
Lu Guo
Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, No. 199, Donggang West Rd., Lanzhou 730000, China
Yu Dong
Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, No. 199, Donggang West Rd., Lanzhou 730000, China
Tingrui Bao
Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, No. 199, Donggang West Rd., Lanzhou 730000, China
Huiyuan Wang
Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, No. 199, Donggang West Rd., Lanzhou 730000, China
Tao Xu
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
Ying Zhang
State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China
Jian Han
Department of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, No. 199, Donggang West Rd., Lanzhou 730000, China
Staphylococcus aureus can cause chronic infections which are closely related to persister formation. Purine metabolism is involved in S. aureus persister formation, and purN, encoding phosphoribosylglycinamide formyltransferase, is an important gene in the purine metabolism process. In this study, we generated a ΔpurN mutant of the S. aureus Newman strain and assessed its roles in antibiotic tolerance and virulence. The ΔpurN in the late exponential phase had a significant defect in persistence to antibiotics. Complementation of the ΔpurN restored its tolerance to different antibiotics. PurN significantly affected virulence gene expression, hemolytic ability, and biofilm formation in S. aureus. Moreover, the LD50 (3.28 × 1010 CFU/mL) of the ΔpurN for BALB/c mice was significantly higher than that of the parental strain (2.81 × 109 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 ΔpurN 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 S. aureus persisters via GltB and regulates its virulence by activating the SaeRS two-component system.
