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bioRxiv · 10.1101/2024.09.23.613229

A Novel Adhesin of B. pertussis is Key to Colonisation of Epithelial Cells

Abstract

Despite effective vaccines to protect against Whooping cough, or pertussis, the disease is resurgent in many countries. A switch from acellular to whole-cell vaccines has resulted in waning protective immunity, likely contributing to increases in infection prevalence, underlining the need to better understand B. pertussis virulence. As a respiratory pathogen, B. pertussis colonises the upper respiratory tract utilising an array of adhesins, four of which (FHA, pertactin, Fim2/3) are included in the acellular vaccine. In this study, we identified two Bvg regulated genes that are upregulated during virulence conditions and thus potentially involved in pathogenesis. bp1251 and bp1252 encode orphan toxin B subunits, with homology to AB toxin B subunits. Mutation of bp1251 and bp1252 reduced the in vitro adherence of B. pertussis to A549 and BEAS-2B alveolar and bronchial epithelial-like cells. In a murine model of infection, bp1251 and bp1252 mutant strains were recovered from the nasal cavity and lungs at lower levels than WT. In vitro no effect of mutation of bp1251 or bp1252 on cell invasion or toxicity was found suggesting that these proteins do not form part of a toxin. Given their homology to B subunits of AB toxins, and their role in colonisation, we propose that BP1251 and BP1252 are novel adhesins. Our data suggests that these proteins play a significant role in Bordetella infection and have the potential to further the understanding of B. pertussis pathogenesis.

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Gollan, M., Gestal, M. C., Parrish, K. M., Harvill, E. T., Preston, A., MacArthur, I.. 2024-09-23. A Novel Adhesin of B. pertussis is Key to Colonisation of Epithelial Cells. https://doi.org/10.1101/2024.09.23.613229

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