Revisiting the regulation of the capsular polysaccharide biosynthesis gene cluster in Staphylococcus aureus. Issue 4 (25th July 2019)

• Record Type: Journal Article
• Authors: Keinhörster, Daniela; Salzer, Andrea; Duque‐Jaramillo, Alejandra; George, Shilpa E.; Marincola, Gabriella; Lee, Jean C.; Weidenmaier, Christopher; Wolz, Christiane
• Is Part Of: Molecular microbiology. Volume 112:Issue 4(2019)
• Page Start: 1083
• Page End: 1099
• Publication Date: 2019-07-25
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14347
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: Capsular polysaccharide (CP) biosynthesis in Staphylococcus aureus is tightly controlled resulting in a heterogeneous phenotype within a population and CP being mainly detectable in nongrowing cells. Expression of the corresponding biosynthesis gene cluster is driven by one promoter element (P cap ). Here, we demonstrate that P cap contains a main SigB‐dependent promoter. The SigB consensus motif overlaps with a previously described inverted repeat (IR) that is crucial for cap expression. The essentiality of the IR is derived from this region acting as a SigB binding site rather than as an operator site for the proposed cap activators RbsR and MsaB. Furthermore, P cap contains an extensive upstream region harboring a weak SigA‐dependent promoter and binding sites for cap repressors such as SaeR, CodY and Rot. Heterogeneous CP synthesis is determined by SigB activity and repressor binding to the upstream region. SigB dependency and regulation by the upstream repressors are also sufficient to explain the temporal gene expression pattern at the transcriptional level. However, CP synthesis remains growth phase‐dependent even when transcription is rendered constitutive, suggesting additional posttranscriptional regulatory circuits. Thus, the interference of multiple repressors with SigB‐dependent promoter activity as well as post‐transcriptional mechanisms ensure the appropriate regulation of CP synthesis. Abstract : The capsular polysaccharide biosynthesis gene cluster in Staphylococcus aureus is regulated by one principal promoter element P cap . P cap contains a main SigB‐dependent promoter and a second weak SigA‐dependent promoter further upstream. However, the P cap upstream region mainly functions as binding site for regulators such as Rot, CodY and Sae. Interference of these repressors with SigB‐dependent promoter activity as well as post‐transcriptional mechanisms ensure the typical heterogeneous and temporal CP synthesis.