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

• Published in: PLoS pathogens 2022-04, Vol.18 (4), p.e1010402
• Main Authors: Holubova, Jana, Stanek, Ondrej, Juhasz, Attila, Hamidou Soumana, Illiassou, Makovicky, Peter, Sebo, Peter
• Format: Article
• Language: English
• Subjects: Adenylate cyclase; Adenylate Cyclase Toxin; Adhesins; Adhesins, Bacterial - metabolism; Aerosols; Animal models; Animals; Bacteria; Biology and Life Sciences; Bordetella pertussis; Bordetella pertussis - genetics; Catarrh; Disease Models, Animal; Disease transmission; Genetic aspects; Genotype; Health aspects; Hemagglutinins; Host-bacteria relationships; Humans; Identification and classification; Immunization; Immunocompetence; Immunodeficiency; Infant mortality; Infections; Lungs; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mucosa; Mutants; MyD88 protein; Myeloid Differentiation Factor 88; Nasal Cavity - microbiology; Nose; Pathogens; Pertussis; Pertussis toxin; Pertussis Vaccine; Pili; Pneumonia; Research and Analysis Methods; Rhinosinusitis; Shedding; Toxins; Vaccines; Virulence; Virulence (Microbiology); Virulence factors; Virulence Factors, Bordetella - genetics; Whooping cough; Whooping Cough - transmission
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 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.