Combined RNAseq and ChIPseq Analyses of the BvgA Virulence Regulator of Bordetella pertussis

Abstract

Bordetella pertussis , the etiological agent of whooping cough, remains a major global health problem. Despite the global usage of whole-cell vaccines since the 1950s and of acellular vaccines in the 1990s, it still is one of the most prevalent vaccine-preventable diseases in industrialized countries. Virulence of B. pertussis is controlled by BvgA/S, a two-component system responsible for upregulation of virulence-activated genes ( vag s) and downregulation of virulence-repressed genes ( vrg s). By transcriptome sequencing (RNAseq) analyses, we identified more than 270 vag s or vrg s, and chromatin immunoprecipitation sequencing (ChIPseq) analyses revealed 148 BvgA-binding sites, 91 within putative promoter regions, 52 within open reading frames, and 5 in noncoding regions. Some vag s, such as dnt and fhaL , do not contain a BvgA-binding site, suggesting indirect regulation. In contrast, several vrg s and some genes not identified by RNAseq analyses under laboratory conditions contain strong BvgA-binding sites, indicating previously unappreciated complexities of BvgA/S biology.