Pertactin contributes to shedding and transmission of Bordetella bronchiseptica.

Autor: Ma L; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America., Dewan KK; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America., Taylor-Mulneix DL; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America., Wagner SM; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America., Linz B; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America., Rivera I; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America., Su Y; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.; Department of Biochemistry, University of Georgia, Athens, Georgia, United States of America., Caulfield AD; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America., Blas-Machado U; Department of Pathology, Athens Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America., Harvill ET; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2021 Aug 04; Vol. 17 (8), pp. e1009735. Date of Electronic Publication: 2021 Aug 04 (Print Publication: 2021).
DOI: 10.1371/journal.ppat.1009735
Abstrakt: Whooping cough is resurging in the United States despite high vaccine coverage. The rapid rise of Bordetella pertussis isolates lacking pertactin (PRN), a key vaccine antigen, has led to concerns about vaccine-driven evolution. Previous studies showed that pertactin can mediate binding to mammalian cells in vitro and act as an immunomodulatory factor in resisting neutrophil-mediated clearance. To further investigate the role of PRN in vivo, we examined the functions of pertactin in the context of a more naturally low dose inoculation experimental system using C3H/HeJ mice that is more sensitive to effects on colonization, growth and spread within the respiratory tract, as well as an experimental approach to measure shedding and transmission between hosts. A B. bronchiseptica pertactin deletion mutant was found to behave similarly to its wild-type (WT) parental strain in colonization of the nasal cavity, trachea, and lungs of mice. However, the pertactin-deficient strain was shed from the nares of mice in much lower numbers, resulting in a significantly lower rate of transmission between hosts. Histological examination of respiratory epithelia revealed that pertactin-deficient bacteria induced substantially less inflammation and mucus accumulation than the WT strain and in vitro assays verified the effect of PRN on the induction of TNF-α by murine macrophages. Interestingly, only WT B. bronchiseptica could be recovered from the spleen of infected mice and were further observed to be intracellular among isolated splenocytes, indicating that pertactin contributes to systemic dissemination involving intracellular survival. These results suggest that pertactin can mediate interactions with immune cells and augments inflammation that contributes to bacterial shedding and transmission between hosts. Understanding the relative contributions of various factors to inflammation, mucus production, shedding and transmission will guide novel strategies to interfere with the reemergence of pertussis.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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