PurN Is Involved in Antibiotic Tolerance and Virulence in Staphylococcus aureus

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 Delta purN mutant of the S. aureus Newman strain and assessed its roles in antibiotic tolerance and virulence. The Delta purN in the late exponential phase had a significant defect in persistence to antibiotics. Complementation of the Delta purN 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 x 10(10) CFU/mL) of the Delta purN for BALB/c mice was significantly higher than that of the parental strain (2.81 x 10(9) 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 Delta purN 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.

Automated summary

This study demonstrates the role of PurN in the formation of late exponential phase Staphylococcus aureus persisters and its regulation of virulence through GltB and the SaeRS two-component system.