Oral immunization with a dam mutant of Yersinia pseudotuberculosis protects against plague


Taylor, VL; Titball, RW; Oyston, PC; (2005) Oral immunization with a dam mutant of Yersinia pseudotuberculosis protects against plague. Microbiology (Reading, England), 151 (Pt 6). pp. 1919-26. ISSN 1350-0872 DOI: 10.1099/mic.0.27959-0

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Abstract

: Inactivation of the gene encoding DNA adenine methylase (dam) has been shown to attenuate some pathogens such as Salmonella enterica serovar Typhimurium and is a lethal mutation in others such as Yersinia pseudotuberculosis strain YPIII. In this study the dam methylase gene in Yersinia pseudotuberculosis strain IP32953 was inactivated. Unlike the wild-type, DNA isolated from the mutant could be digested with MboI, which is consistent with an altered pattern of DNA methylation. The mutant was sensitive to bile salts but not to 2-aminopurine. The effect of dam inactivation on gene expression was examined using a DNA microarray. In BALB/c mice inoculated orally or intravenously with the dam mutant, the median lethal dose (MLD) was at least 10(6)-fold higher than the MLD of the wild-type. BALB/c mice inoculated with the mutant were protected against a subcutaneous challenge with 100 MLDs of Yersinia pestis strain GB and an intravenous challenge with 300 MLDs of Y. pseudotuberculosis IP32953.<br/>

Item Type: Article
Keywords: Dna adenine methylase, escherichia-coli, salmonella-, typhimurium, suicide vector, v-antigen, pestis, virulence, gene, construction, expression
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Vaccine Centre
PubMed ID: 15941999
Web of Science ID: 230041200019
URI: http://researchonline.lshtm.ac.uk/id/eprint/13391

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