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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, Audra R; Gutierrez-Ferman, Jessica L; Yount, Kacy S; Love, Cheraton F; Choi, Hyun G; Vargas, Mario A; Raju, Deepa; Corps, Kara N; Howell, P Lynne; Dubey, Purnima; Deora, Rajendar.
Afiliação
  • Fullen AR; The Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America.
  • Gutierrez-Ferman JL; The Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America.
  • Yount KS; The Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America.
  • Love CF; Department of Microbiology and Immunology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America.
  • Choi HG; The Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America.
  • Vargas MA; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Raju D; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Corps KN; Department of Veterinary Biosciences, Comparative Pathology and Digital Imaging Shared Resource, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States of America.
  • Howell PL; Program in Molecular Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
  • Dubey P; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
  • Deora R; The Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States of America.
PLoS Pathog ; 18(8): e1010764, 2022 08.
Article em En | MEDLINE | ID: mdl-35969621
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-ß-1,6-N-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 released 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. 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. These studies can serve as a foundation for other PNAG/PGA polysaccharides and for the development of an effective Bp vaccine that includes Bps.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Coqueluche / Infecções por Escherichia coli Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Coqueluche / Infecções por Escherichia coli Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article