The effect of iron availability on transcription of the Neisseria meningitidis fHbp gene varies among clonal complexes

Holly Sanders,Ian M Feavers,Martin C J Maiden,Carina Brehony,Caroline Vipond

doi:10.1099/mic.0.054957-0

Holly Sanders, Ian M Feavers + Show 3 more

Open Access

https://doi.org/10.1099/mic.0.054957-0

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Abstract

Factor H binding protein (fHbp) is a major antigenic component of novel vaccines designed to protect against meningococcal disease. Prediction of the potential coverage of these vaccines is difficult, as fHbp is antigenically variable and levels of expression differ among isolates. Transcriptional regulation of the fHbp gene is poorly understood, although evidence suggests that oxygen availability is involved. In this study iron accessibility was found to affect fHbp transcription. However, regulation differed among meningococcal clonal complexes (ccs). For the majority of isolates, increased iron concentrations upregulated transcription. This effect was enhanced by the presence of a 181 bp insertion element upstream of fHbp, associated with isolates belonging to cc4 and cc5. Conversely, meningococci belonging to cc32 showed iron-repressed control of fHbp, as regulation was dominated by cotranscription with the iron-repressed upstream gene cbbA. These results highlight the complexity of fHbp regulation and demonstrate that control of transcription can vary among genetic lineages.

Highlights

Neisseria meningitidis, the meningococcus, is a major cause of bacterial meningitis and septicaemia
The factor H binding protein (fHbp) of N. meningitidis is a component of two vaccines developed ostensibly to control serogroup B meningococcal disease (Donnelly et al, 2010; Jiang et al, 2010)
To evoke an effective bactericidal response against the meningococcus, it is critical that sufficient fHbp is expressed on the surface of the bacterium (Koeberling et al, 2011), and there is evidence that the level of expression of the protein on the bacterial surface correlates with the susceptibility of target isolates to fHbp-specific antibodies in an serum bactericidal assay (SBA) (Jiang et al, 2010)

Summary

Introduction

The meningococcus, is a major cause of bacterial meningitis and septicaemia. The development of a vaccine with the potential to protect against organisms expressing the group B capsule has focussed on subcapsular protein antigens. One such antigen is factor H binding protein (fHbp), a surfaceexposed lipoprotein that is a major component of two vaccine candidates: Bexsero (Novartis) and rLP2086 (Pfizer). Both are at an advanced stage of clinical

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