Abstract
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 β-lactam resistance regulators. Interestingly, we observed a complex interplay between virulence regulation, β-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.
Highlights
Methicillin-resistant Staphylococcus aureus (MRSA) infection is an epidemic health threat and a major worldwide healthcare burden[1,2,3]
Variants on sprA and clumping factor B may be an origin of distinct virulence characteristic of the strain, because sprA encodes both an non-coding RNA (ncRNA) and a small internal cytolytic peptide[25], and clumping factor B is related to colonization[26,27]
The primary transcriptome architecture of the strain was determined based on a total of 1,861 transcription start sites (TSSs) detected under the four experimental conditions used
Summary
Methicillin-resistant Staphylococcus aureus (MRSA) infection is an epidemic health threat and a major worldwide healthcare burden[1,2,3]. To elucidate the genetic basis of drug resistance, virulence, and pathogenesis, genomes of hundreds of S. aureus isolates have been sequenced and analyzed, showing that the characteristics of S. aureus are different from strain to strain, even in different strains isolated from the same origin[4,5,6,7,8]. Expression and production of virulence factors are tightly regulated by variety of elements such as transcriptional regulators, quorum-sensing, and regulatory RNAs in pathogenic bacteria[15,16,17]. The architecture of transcriptional and translational signals, represented by promoters, cis-acting elements, SD sequences, and regulatory 5′UTR sequences, can be identified with various computational toolboxes from experimentally determined transcription start sites (TSSs)[20,21,22]. With the genome-wide determination of TSSs, we identified principal elements of gene expression, such as promoters and SD sequences, regulatory RNA elements, and unannotated transcripts. We examined strain’s response to antibiotic treatments to investigate genes associated with drug resistance and the regulatory framework that orchestrates gene expression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
