RESUMO
Pertussis toxin is produced by the causative agent of whooping cough, Bordetella pertussis, and is an adenosine diphosphate (ADP)-ribosyltransferase capable of covalently modifying and thereby inactivating many eukaryotic G proteins involved in cellular metabolism. The toxin is a principal determinant of virulence in whooping cough and is a primary candidate for an acellular pertussis vaccine, yet it is unclear whether the ADP-ribosyltransferase activity is required for both pathogenic and immunoprotective activities. A B. pertussis strain that produced an assembled pertussis holotoxin with only 1 percent of the ADP-ribosyltransferase activity of the native toxin was constructed and was found to be deficient in pathogenic activities associated with B. pertussis including induction of leukocytosis, potentiation of anaphylaxis, and stimulation of histamine sensitivity. Moreover, this mutant strain failed to function as an adjuvant and was less effective in protecting mice from intracerebral challenge infection. These data suggest that the ADP-ribosyltransferase activity is necessary for both pathogenicity and optimum immunoprotection. These findings bear directly on the design of a nontoxic pertussis vaccine.
Assuntos
Bordetella pertussis/imunologia , Pentosiltransferases/metabolismo , Toxina Pertussis , Fatores de Virulência de Bordetella/metabolismo , ADP Ribose Transferases , Adjuvantes Imunológicos , Anafilaxia/etiologia , Animais , Antígenos/imunologia , Bordetella pertussis/enzimologia , Bordetella pertussis/genética , Códon , Tolerância a Medicamentos , Histamina/farmacologia , Imunização , Leucocitose/etiologia , Substâncias Macromoleculares , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mutação , Ovalbumina/imunologia , Fatores de Virulência de Bordetella/genética , Fatores de Virulência de Bordetella/imunologiaRESUMO
The ability of three isolates of serogroup 1 and one isolate of serogroup 4 of Legionnaires' disease bacterium (LDB) to infect and cause fever and death in guinea pigs was studied, as well as their ability to produce plaques in cultured primary chick embryo cells. The serogroup 4 isolate originally was recovered from cord clot and placental tissue from a healthy mother following delivery of a normal child. The effects on LDB of prolonged cultivation on supplemented Mueller-Hinton (MH) agar medium and of subsequent cultivation in yolk sacs of chick embryos were examined. Prolonged cultivation of LDB on MH medium resulted in great loss of ability to produce plaques and to cause fever and death in guinea pigs. Subsequent passage in embryonated eggs of MH-adapted LDB tended to restore ability to produce plaques and to cause infection and illness in guinea pigs. Fatty acid composition profiles of the four strains were similar to each other.