Genome-scale analysis of Methicillin-resistant Staphylococcus aureus USA300 reveals a tradeoff between pathogenesis and drug resistance

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Staphylococcus aureus infection is a rising public health care threat. S. aureus is believed to have elaborate regulatory networks that orchestrate its virulence. Despite its importance, the systematic understanding of the transcriptional landscape of S. aureus is limited. Here, we describe the primary transcriptome landscape of an epidemic USA300 isolate of community-acquired methicillin-resistant S. aureus. We experimentally determined 1,861 transcription start sites with their principal promoter elements, including well-conserved -35 and -10 elements and weakly conserved -16 element and 5' untranslated regions containing AG-rich Shine-Dalgarno sequence. In addition, we identified 225 genes whose transcription was initiated from multiple transcription start sites, suggesting potential regulatory functions at transcription level. Along with the transcription unit architecture derived by integrating the primary transcriptome analysis with operon prediction, the measurement of differential gene expression revealed the regulatory framework of the virulence regulator Agr, the SarA-family transcriptional regulators, and beta-lactam resistance regulators. Interestingly, we observed a complex interplay between virulence regulation, beta-lactam resistance, and metabolism, suggesting a possible tradeoff between pathogenesis and drug resistance in the USA300 strain. Our results provide platform resource for the location of transcription initiation and an in-depth understanding of transcriptional regulation of pathogenesis, virulence, and antibiotic resistance in S. aureus.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2018-02
Language
English
Article Type
Article
Keywords

TRANSCRIPTIONAL START SITES; RNA SECONDARY STRUCTURE; CLUMPING FACTOR-B; SIGMA(B) REGULON; NASAL COLONIZATION; BACILLUS-SUBTILIS; EXPRESSION; VIRULENCE; AGR; PROTEINS

Citation

SCIENTIFIC REPORTS, v.8

ISSN
2045-2322
DOI
10.1038/s41598-018-20661-1
URI
http://hdl.handle.net/10203/240373
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
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