Abstract
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 (Pcap ). Here, we demonstrate that Pcap 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, Pcap 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.
Highlights
Staphylococcus aureus is an opportunistic pathogen that asymptomatically colonizes parts of the human population, thereby increasing the risk of subsequent infections.Its capacity to cause a wide variety of diseases depends on secreted virulence factors as well as cell surface attached proteins and polysaccharides [1,2,3]
This Sigma factor B (SigB) promoter consists of a conserved SigB -35 motif (GTTTAA) and a -10 region harboring three mismatches (ATGTAA versus GGGTAT) [51]
The SigB -35 consensus sequence is located within the inverted repeat (IR) that is crucial for principal promoter element (Pcap) activity [12]
Summary
Staphylococcus aureus is an opportunistic pathogen that asymptomatically colonizes parts of the human population, thereby increasing the risk of subsequent infections.Its capacity to cause a wide variety of diseases depends on secreted virulence factors as well as cell surface attached proteins and polysaccharides [1,2,3]. The capsular polysaccharide (CP) is one of these cell surface structures playing an important role in S. aureus pathogenesis and bacterial evasion of the host immune defences [3, 4]. It is being discussed as a target for immunotherapy and as a vaccine candidate [5]. CP serotypes 5 and 8 are the two main CP serotypes produced by S. aureus strains [6,7,8,9] Their structure is highly similar due to the closely related cap and cap gene clusters. Not all bacteria in a population are CP-
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