1. An aromatic amino acid auxotrophic mutant of Bordetella bronchiseptica is attenuated and immunogenic in a mouse model of infection
- Author
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McArthur, JD, West, NP, Cole, JN, Jungnitz, H, Guzmán, CA, Chin, J, Lehrbach, PR, Djordjevic, SP, and Walker, MJ
- Subjects
Mice, Inbred BALB C ,Alkyl and Aryl Transferases ,Macrophages ,Vaccination ,Molecular Sequence Data ,Sequence Analysis, DNA ,respiratory system ,Bordetella bronchiseptica ,Vaccines, Attenuated ,Lymphocyte Activation ,Microbiology ,Antibodies, Bacterial ,Cell Line ,Mice ,Disease Models, Animal ,Amino Acids, Aromatic ,Bacterial Vaccines ,Mutation ,Operon ,otorhinolaryngologic diseases ,Animals ,Female ,3-Phosphoshikimate 1-Carboxyvinyltransferase ,Bordetella Infections ,Anthranilate Synthase - Abstract
We have constructed an aromatic amino acid auxotrophic mutant of Bordetella bronchiseptica, harbouring mutations in aroA and trpE to investigate the use of such a strain as a live-attenuated vaccine. B. bronchiseptica aroA trpE was unable to grow in minimal medium without aromatic supplementation. Compared to the parental wild-type strain, the mutant displayed significantly reduced abilities to invade and survive within the mouse macrophage-like cell line J774A.1 in vitro and in the murine respiratory tract following experimental intranasal infection. Mice vaccinated with B. bronchiseptica aroA trpE displayed significant dose-dependent increases in B. bronchiseptica-specific antibody responses, and exhibited increases in the number of B. bronchiseptica-reactive spleen cells in lymphoproliferation assays. Immunised animals were protected against lung colonisation after challenge with the wild-type parental strain. With such a broad host range displayed by B. bronchiseptica, the attenuated strain constructed in this study may not only be used for the prevention of B. bronchiseptica-associated disease, but also for the potential delivery of heterologous antigen. © 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.
- Published
- 2003