A Novel LysR-Type Global Regulator RpvA Controls Persister Formation and Virulence in Staphylococcus aureus
Staphylococcus aureus is the leading cause of wound and nosocomial infections. Persister formation and virulence factors play crucial roles during S. aureus infection. However, the mechanisms of persister formation and its relationship to virulence in S. aureus are poorly understood. In this study, we screened a transposon mutant library and identified a LysR-type global transcriptional regulator NWMN_0037, which we called RpvA, for regulator of persistence and virulence, whose mutation leads to higher susceptibility to antibiotics ampicillin and norfloxacin and various stresses including oxidative stress, heat, and starvation in late exponential and early stationary phase. Interestingly, the rpvA mutant was highly attenuated for virulence compared with the parent S. aureus Newman strain as shown by a much higher lethal dose, reduced ability to survive in macrophages and to form abscess in the mouse model. Transcriptional profiling and metabolomic analysis revealed that RpvA could repress multiple genes including gapR, gapA, tpi, pgm, eno, glpD, and acs expression and enhance production of numerous intermediate metabolites including dihydroxyacetone phosphate, 2-phosphoglycerate, acetyl-CoA, glycerol 3-phosphate, L-glutamate in the cells. The differentially expressed genes and altered production of metabolites are distributed in global metabolism including carbohydrate metabolism, amino acid metabolism, energy metabolism and metabolism of cofactors and vitamins. These metabolic adjustments could cause the cell to go into dormancy, thus promoting S. aureus to convert to persisters. In addition, RpvA could upregulate the expression of virulence genes including hla, hlgA, hlgB, hlgC, lukF, lukS, lukD, sea and coa, and carotenoid biosynthesis genes (crtI, crtM, crtN). Gel shift assay confirmed that RpvA could bind to the promoters of candidate target genes hla, hlgB and crtM, thus promoting S. aureus virulence. Because of the important functions of the RpvA, it may serve as an attractive target for developing new drugs and vaccines to more effectively control S. aureus infections.
- Downloaded 159 times
- Download rankings, all-time:
- Site-wide: 98,750 out of 118,150
- In microbiology: 7,402 out of 9,341
- Year to date:
- Site-wide: 76,371 out of 118,150
- Since beginning of last month:
- Site-wide: 53,448 out of 118,150
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!