Characterization and immunogenicity of Salmonella typhimurium SL1344 and UK-1 Δcrp and Δcdt deletion mutants

X. Zhang, S. M. Kelly, W. S. Bollen, R. Curtiss

Research output: Contribution to journalArticle

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Abstract

S. typhimurium SL1344 and UK-1 mutants with deletions of the crp (cyclic AMP receptor protein) and cdt (colonization of deep tissues) genes have been constructed and characterized, and their levels of virulence and immunogenicity have been determined for BALB/c mice. All Crp- Cdt- and Crp+ Cdt- mutants were avirulent, as mice survived oral doses of 109 cells without illness. All the mutants colonized the gut-associated lymphoid tissue efficiently, but capacities to colonize deeper tissues, such as those of the spleen and liver, and blood were significantly reduced for the Crp- Cdt- and Crp+ Cdt- mutants compared with the Crp- Cdt+ mutant and the wild- type parent strain. The Crp- Cdt- and Crp+ Cdt- SL1344 strains induced complete protection, as all mice immunized with the mutants survived challenge with ~104 times the 50% lethal dose of the wild-type SL1344 strain. The Crp- UK-1 strain was least attenuated yet induced the highest level of protective immunity against challenge with the wild-type UK-1 strain. The Crp+ Cdt- and Crp- Cdt- strains, although totally attenuated, differed in immunogenicity to challenge with the highly virulent UK-1 parent, with the apparently hyperattenuated Crp- Cdt- strain inducing a lower level of protective immunity than the Crp+ Cdt- strain. Nevertheless, these UK-1 Crp- Cdt- and Crp+ Cdt- strains induced complete protective immunity to challenge with the less-virulent SL1344 wild-type strain. Taken collectively, the results indicate that the attenuation of a highly virulent S. typhimurium strain can yield a vaccine that induces excellent protective immunity to challenge with less-virulent S. typhimurium strains.

Original languageEnglish (US)
Pages (from-to)5381-5387
Number of pages7
JournalInfection and Immunity
Volume65
Issue number12
StatePublished - 1997
Externally publishedYes

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Cyclic AMP Receptor Protein
Salmonella typhimurium
Immunity
Lethal Dose 50
Lymphoid Tissue
Virulence
Vaccines
Spleen
UK 1
Liver
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Characterization and immunogenicity of Salmonella typhimurium SL1344 and UK-1 Δcrp and Δcdt deletion mutants. / Zhang, X.; Kelly, S. M.; Bollen, W. S.; Curtiss, R.

In: Infection and Immunity, Vol. 65, No. 12, 1997, p. 5381-5387.

Research output: Contribution to journalArticle

Zhang, X, Kelly, SM, Bollen, WS & Curtiss, R 1997, 'Characterization and immunogenicity of Salmonella typhimurium SL1344 and UK-1 Δcrp and Δcdt deletion mutants', Infection and Immunity, vol. 65, no. 12, pp. 5381-5387.
Zhang, X. ; Kelly, S. M. ; Bollen, W. S. ; Curtiss, R. / Characterization and immunogenicity of Salmonella typhimurium SL1344 and UK-1 Δcrp and Δcdt deletion mutants. In: Infection and Immunity. 1997 ; Vol. 65, No. 12. pp. 5381-5387.
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abstract = "S. typhimurium SL1344 and UK-1 mutants with deletions of the crp (cyclic AMP receptor protein) and cdt (colonization of deep tissues) genes have been constructed and characterized, and their levels of virulence and immunogenicity have been determined for BALB/c mice. All Crp- Cdt- and Crp+ Cdt- mutants were avirulent, as mice survived oral doses of 109 cells without illness. All the mutants colonized the gut-associated lymphoid tissue efficiently, but capacities to colonize deeper tissues, such as those of the spleen and liver, and blood were significantly reduced for the Crp- Cdt- and Crp+ Cdt- mutants compared with the Crp- Cdt+ mutant and the wild- type parent strain. The Crp- Cdt- and Crp+ Cdt- SL1344 strains induced complete protection, as all mice immunized with the mutants survived challenge with ~104 times the 50{\%} lethal dose of the wild-type SL1344 strain. The Crp- UK-1 strain was least attenuated yet induced the highest level of protective immunity against challenge with the wild-type UK-1 strain. The Crp+ Cdt- and Crp- Cdt- strains, although totally attenuated, differed in immunogenicity to challenge with the highly virulent UK-1 parent, with the apparently hyperattenuated Crp- Cdt- strain inducing a lower level of protective immunity than the Crp+ Cdt- strain. Nevertheless, these UK-1 Crp- Cdt- and Crp+ Cdt- strains induced complete protective immunity to challenge with the less-virulent SL1344 wild-type strain. Taken collectively, the results indicate that the attenuation of a highly virulent S. typhimurium strain can yield a vaccine that induces excellent protective immunity to challenge with less-virulent S. typhimurium strains.",
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