Abstract
We have constructed a dam mutant of Yersinia pestis GB. In BALB/c mice inoculated subcutaneously, the median lethal dose of the mutant was at least 2000-fold higher than the wild type. Mice inoculated with sub-lethal doses of the mutant were protected against a subsequent challenge with virulent Y. pestis. The effect of dam inactivation on gene expression was examined using a DNA microarray, which revealed increased expression of a number of genes associated with the SOS response. These results confirm the key role of Dam in the regulation of virulence, and its potential role as a target for the generation of attenuated strains of pathogenic bacteria.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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DNA Methylation
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Disease Models, Animal
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Female
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Gene Deletion*
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Gene Expression Regulation, Bacterial
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Mice
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Mice, Inbred BALB C
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Mutagenesis, Insertional
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Oligonucleotide Array Sequence Analysis
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Plague / prevention & control*
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Plague Vaccine / genetics
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Plague Vaccine / immunology*
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SOS Response, Genetics
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Site-Specific DNA-Methyltransferase (Adenine-Specific) / genetics*
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Site-Specific DNA-Methyltransferase (Adenine-Specific) / physiology
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Survival Analysis
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Vaccines, Attenuated / administration & dosage
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Vaccines, Attenuated / immunology
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Virulence / genetics
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Yersinia pestis / genetics
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Yersinia pestis / pathogenicity*
Substances
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Plague Vaccine
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Vaccines, Attenuated
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Site-Specific DNA-Methyltransferase (Adenine-Specific)