The Fim and FhaB adhesins play a crucial role in nasal cavity infection and Bordetella pertussis transmission in a novel mouse catarrhal infection model

0563496 - MBÚ 2023 RIV US eng J - Článek v odborném periodiku
Holubová, Jana - Staněk, Ondřej - Juhasz, Attila - Soumana, I. H. - Makovický, Peter - Šebo, Peter
The Fim and FhaB adhesins play a crucial role in nasal cavity infection and Bordetella pertussis transmission in a novel mouse catarrhal infection model.
PLoS Pathogens. Roč. 18, č. 4 (2022), č. článku e1010402. ISSN 1553-7366. E-ISSN 1553-7374
Grant CEP: GA ČR(CZ) GX19-27630X; GA MŠMT(CZ) LM2018133; GA MŠMT(CZ) LM2018126; GA MŠMT EF18_046/0015861; GA MŠMT ED2.1.00/19.0395; GA MŠMT(CZ) ED1.1.00/02.0109
Výzkumná infrastruktura: EATRIS-CZ III - 90133; CCP II - 90126
Institucionální podpora: RVO:61388971 ; RVO:68378050
Klíčová slova: adenylate-cyclase toxin * serum antibody-responses * neutrophil recruitment * confers resistance * baboon model * whole-cell * antigen * vaccine * colonization * protection
Obor OECD: Microbiology; Microbiology (UMG-J)
Impakt faktor: 6.7, rok: 2022
Způsob publikování: Open access
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010402

Pulmonary infections caused by Bordetella pertussis used to be the prime cause of infant mortality in the pre-vaccine era and mouse models of pertussis pneumonia served in characterization of B. pertussis virulence mechanisms. However, the biologically most relevant catarrhal disease stage and B. pertussis transmission has not been adequately reproduced in adult mice due to limited proliferation of the human-adapted pathogen on murine nasopharyngeal mucosa. We used immunodeficient C57BL/6J MyD88 KO mice to achieve B. pertussis proliferation to human-like high counts of 108 viable bacteria per nasal cavity to elicit rhinosinusitis accompanied by robust shedding and transmission of B. pertussis bacteria to adult co-housed MyD88 KO mice. Experiments with a comprehensive set of B. pertussis mutants revealed that pertussis toxin, adenylate cyclase toxin-hemolysin, the T3SS effector BteA/BopC and several other known virulence factors were dispensable for nasal cavity infection and B. pertussis transmission in the immunocompromised MyD88 KO mice. In contrast, mutants lacking the filamentous hemagglutinin (FhaB) or fimbriae (Fim) adhesins infected the nasal cavity poorly, shed at low levels and failed to productively infect co-housed MyD88 KO or C57BL/6J mice. FhaB and fimbriae thus appear to play a critical role in B. pertussis transmission. The here-described novel murine model of B. pertussis-induced nasal catarrh opens the way to genetic dissection of host mechanisms involved in B. pertussis shedding and to validation of key bacterial transmission factors that ought to be targeted by future pertussis vaccines.
Trvalý link: https://hdl.handle.net/11104/0335454