RESUMO
Bordetella pertussis, the etiological agent of whooping cough, still causes outbreaks. We recently found evidence that B. pertussis can survive and even replicate inside human macrophages, indicating that this host cell might serve as a niche for persistence. In this work, we examined the interaction of B. pertussis with a human monocyte cell line (THP-1) that differentiates into macrophages in culture in order to investigate the host cell response to the infection and the mechanisms that promote that intracellular survival. To that end, we investigated the expression profile of a selected number of genes involved in cellular bactericidal activity and the inflammatory response during the early and late phases of infection. The bactericidal and inflammatory response of infected macrophages was progressively downregulated, while the number of THP-1 cells heavily loaded with live bacteria increased over time postinfection. Two of the main toxins of B. pertussis, pertussis toxin (Ptx) and adenylate cyclase (CyaA), were found to be involved in manipulating the host cell response. Therefore, failure to express either toxin proved detrimental to the development of intracellular infections by those bacteria. Taken together, these results support the relevance of host defense gene manipulation to the outcome of the interaction between B. pertussis and macrophages.
Assuntos
Bordetella pertussis/imunologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Coqueluche/genética , Coqueluche/imunologia , Bordetella pertussis/genética , Linhagem Celular , Citocinas/genética , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/genética , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Macrófagos/microbiologia , Viabilidade Microbiana/imunologia , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/microbiologia , Fagocitose , Fatores de Virulência/genética , Coqueluche/microbiologiaRESUMO
There has been a resurgence in the number of pertussis cases in Brazil and around the world. Here, the genome of a clinical Bordetella pertussis strain (Bz181) that was recently isolated in Brazil is reported. Analysis of the virulence-associated genes defining the pre- and post-vaccination lineages revealed the presence of the prn2-ptxS1A-fim3B-ptxP3 allelic profile in Bz181, which is characteristic of the current pandemic lineage. A putative metallo-ß-lactamase gene presenting all of the conserved zinc-binding motifs that characterise the catalytic site was identified, in addition to a multidrug efflux pump of the RND family that could confer resistance to erythromycin, which is the antibiotic of choice for treating pertussis disease.
Assuntos
Bordetella pertussis/genética , Genoma Bacteriano , Fatores de Virulência de Bordetella/genética , Coqueluche/microbiologia , Alelos , Bordetella pertussis/classificação , Bordetella pertussis/patogenicidade , Brasil , Humanos , Coqueluche/genéticaRESUMO
There has been a resurgence in the number of pertussis cases in Brazil and around the world. Here, the genome of a clinical Bordetella pertussis strain (Bz181) that was recently isolated in Brazil is reported. Analysis of the virulence-associated genes defining the pre- and post-vaccination lineages revealed the presence of the prn2-ptxS1A-fim3B-ptxP3 allelic profile in Bz181, which is characteristic of the current pandemic lineage. A putative metallo-β-lactamase gene presenting all of the conserved zinc-binding motifs that characterise the catalytic site was identified, in addition to a multidrug efflux pump of the RND family that could confer resistance to erythromycin, which is the antibiotic of choice for treating pertussis disease.
Assuntos
Humanos , Bordetella pertussis/genética , Genoma Bacteriano , Fatores de Virulência de Bordetella/genética , Coqueluche/microbiologia , Alelos , Brasil , Bordetella pertussis/classificação , Bordetella pertussis/patogenicidade , Coqueluche/genéticaRESUMO
Intrafamilial spread of pertussis was evaluated in 21 families (97 individuals) of patients with whooping cough diagnosed by culture or by ELISA serology. During follow-up (average six months), an infectivity rate of 83% was established by an ELISA within these families. However, 46% of the secondary cases were asymptomatic. Most of the asymptomatic cases were in adults or vaccinated children. Unvaccinated infants had classic whooping cough and were exposed to pertussis by their vaccinated siblings or parents. The incidence of classic symptoms of pertussis decreased with age, and atypical pertussis was usually culture negative but rapidly diagnosed by measurement of the IgM- and IgA-class antibodies by ELISA.