RESUMO
Bordetella parapertussis is one of the pathogens that cause whooping cough. Even though its incidence has been rising in the last decades, this species remained poorly investigated. This study reports the first extensive proteome analysis of this bacterium. In an attempt to gain some insight into the infective phenotype, we evaluated the response of B. parapertussis to iron starvation, a critical stress the bacteria face during infection. Among other relevant findings, we observed that the adaptation to this condition involves significant changes in the abundance of two important virulence factors of this pathogen, namely, adenylate cyclase and the O-antigen. We further used the proteomic data to search for B. parapertussis proteins that are absent or classified as pseudogenes in the genome of Bordetella pertussis to unravel differences between both whooping cough causative agents. Among them, we identified proteins involved in stress resistance and virulence determinants that might help to explain the differences in the pathogenesis of these species and the lack of cross-protection of current acellular vaccines. Altogether, these results contribute to a better understanding of B. parapertussis biology and pathogenesis. SIGNIFICANCE: Whooping cough is a reemerging disease caused by both Bordetella pertussis and Bordetella parapertussis. Current vaccines fail to induce protection against B parapertussis and the incidence of this species has been rising over the years. The proteomic analysis of this study provided relevant insights into potential virulence determinants of this poorly-studied pathogen. It further identified proteins produced by B. parapertussis not present in B. pertussis, which might help to explain both the differences on their respective infectious process and the current vaccine failure. Altogether, the results of this study contribute to the better understanding of B. parapertussis pathogenesis and the eventual design of improved preventive strategies against whooping cough.
Assuntos
Bordetella parapertussis/metabolismo , Bordetella pertussis/metabolismo , Deficiências de Ferro , Proteômica/métodos , Fatores de Virulência/metabolismo , Proteínas de Bactérias/análise , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Bordetella parapertussis/efeitos dos fármacos , Bordetella parapertussis/patogenicidade , Bordetella pertussis/patogenicidade , Células Cultivadas , Meios de Cultura/química , Meios de Cultura/farmacologia , Humanos , Ferro/metabolismo , Ferro/farmacologia , Fenótipo , Proteoma/análise , Proteoma/metabolismo , Virulência/efeitos dos fármacosRESUMO
Whooping cough, which is caused by Bordetella pertussis and B. parapertussis, is a reemerging disease. New protective antigens are needed to improve the efficacy of current vaccines against both species. Using proteomic tools, it was here found that B. parapertussis expresses a homolog of AfuA, a previously reported new vaccine candidate against B. pertussis. It was found that this homolog, named AfuABpp , is expressed during B. parapertussis infection, exposed on the surface of the bacteria and recognized by specific antibodies induced by the recombinant AfuA cloned from B. pertussis (rAfuA). Importantly, the presence of the O-antigen, a molecule that has been found to shield surface antigens on B. parapertussis, showed no influence on antibody recognition of AfuABpp on the bacterial surface. The present study further showed that antibodies induced by immunization with the recombinant protein were able to opsonize B. parapertussis and promote bacterial uptake by neutrophils. Finally, it was shown that this antigen confers protection against B. parapertussis infection in a mouse model. Altogether, these results indicate that AfuA is a good vaccine candidate for acellular vaccines protective against both causative agents of whooping cough.
Assuntos
Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Infecções por Bordetella/prevenção & controle , Bordetella parapertussis/efeitos dos fármacos , Bordetella pertussis/genética , Vacina contra Coqueluche/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Infecções por Bordetella/imunologia , Bordetella parapertussis/imunologia , Bordetella parapertussis/patogenicidade , Bordetella pertussis/efeitos dos fármacos , Bordetella pertussis/imunologia , Bordetella pertussis/metabolismo , Modelos Animais de Doenças , Feminino , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Antígenos O/imunologia , Proteômica , Vacinação , Vacinas Acelulares/genética , Vacinas Acelulares/imunologia , Coqueluche/microbiologiaRESUMO
A narrow-spectrum clavulanic acid-inhibited class A beta-lactamase, BOR-1, was identified in a Bordetella bronchiseptica clinical isolate. It shared 45% amino acid identity with L-2 from Stenotrophomonas maltophilia. An identical beta-lactamase gene was found in B. bronchiseptica and Bordetella parapertussis reference strains that may contribute only in part to their resistance phenotype.
