Bps polysaccharide of Bordetella pertussis resists antimicrobial peptides by functioning as a dual surface shield and decoy and converts Escherichia coli into a respiratory pathogen.

Fullen, A. R.; Gutierrez-Ferman, J. L.; Yount, K. S.; Love, C. F.; Choi, H. G.; Vargas, M. A.; Raju, D.; Corps, K. N.; Howell, P. L.; Dubey, P.; Deora, R.

doi:10.1101/2022.04.06.487353

bioRxiv · 10.1101/2022.04.06.487353

Bps polysaccharide of Bordetella pertussis resists antimicrobial peptides by functioning as a dual surface shield and decoy and converts Escherichia coli into a respiratory pathogen.

Fullen, A. R.·Gutierrez-Ferman, J. L.·Yount, K. S.·Love, C. F.·Choi, H. G.·Vargas, M. A.·Raju, D.·Corps, K. N.·Howell, P. L.·Dubey, P.·Deora, R.

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Abstract

Infections and disease caused by the obligate human pathogen Bordetella pertussis (Bp) are increasing, despite widespread vaccinations. The current acellular pertussis vaccines remain ineffective against nasopharyngeal colonization, carriage, and transmission. In this work, we tested the hypothesis that Bordetella polysaccharide (Bps), a member of the poly-{beta}-1,6-A-acetyl-D-glucosamine (PNAG/PGA) family of polysaccharides promotes respiratory tract colonization of Bp by resisting killing by antimicrobial peptides (AMPs). Genetic deletion of the bpsA-D locus, as well as treatment with the specific glycoside hydrolase Dispersin B, increased susceptibility to AMP-mediated killing. Bps was found to be both cell surface-associated and secreted during laboratory growth and mouse infections. Addition of bacterial supernatants containing Bps and purified Bps increased B. pertussis resistance to AMPs. By utilizing ELISA, immunoblot and flow cytometry assays, we show that Bps functions as a dual surface shield and decoy by inhibiting AMP binding. Co-inoculation of C57BL/6J mice with a Bps-proficient strain enhanced respiratory tract survival of the Bps-deficient strain. In combination, the presented results highlight the critical role of Bps as a central driver of B. pertussis pathogenesis. Heterologous production of Bps in a non-pathogenic E. coli K12 strain increased AMP resistance in vitro, and augmented bacterial survival and pathology in the mouse respiratory tract. Therefore, by conferring virulence traits across bacterial genera, Bps transforms a primarily intestinal and urinary tract bacterium into a respiratory pathogen. These studies can serve as a foundation for other PNAG/PGA polysaccharides and for the development of an effective Bp vaccine that includes Bps. Author summaryPertussis or whooping cough, caused by the obligate human pathogen Bordetella pertussis (Bp), is resurging in many countries. Currently, the mechanism by which B. pertussis subverts and resists host immunity is poorly known. In this manuscript, we examined the role of the B. pertussis polysaccharide Bps in promoting resistance to antimicrobial peptides (AMPs), a critical component of host immune defense. We show that the presence of Bps on the bacterial cell surface enhanced AMP resistance. Bps was secreted both during bacterial growth and during mouse infections. We further found that Bps functioned both as a surface shield and decoy, thereby inhibiting AMP binding. Simultaneous infection of mice with Bps-proficient and Bps- deficient strains resulted in greater survival of the Bps-deficient strain in the mouse respiratory tract. Finally, production of Bps in a non-pathogenic E. coli strain increased AMP resistance in vitro, and increased bacterial survival and heightened pathology in the mouse respiratory tract. Our study provides new insights into how B. pertussis has evolved to survive in the mammalian respiratory tract. Additionally, these studies underscore the potential of a single virulence factor to convert a non-pathogenic bacterium into a respiratory tract pathogen.

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Fullen, A. R., Gutierrez-Ferman, J. L., Yount, K. S., Love, C. F., Choi, H. G., Vargas, M. A., Raju, D., Corps, K. N., Howell, P. L., Dubey, P., Deora, R.. 2022-04-06. Bps polysaccharide of Bordetella pertussis resists antimicrobial peptides by functioning as a dual surface shield and decoy and converts Escherichia coli into a respiratory pathogen.. https://doi.org/10.1101/2022.04.06.487353

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