A dam mutant of Yersinia pestis is attenuated and induces protection against plague.
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.
Robinson
Victoria L
VL
Defence Science and Technology Laboratory, Biomedical Sciences, Salisbury, Wilts, UK. vlrobinson@dstl.gov.uk
Oyston
Petra C F
PC
Titball
Richard W
RW
D000818:Animals; D019175:DNA Methylation; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D016254:Mutagenesis, Insertional; D020411:Oligonucleotide Array Sequence Analysis; D010930:Plague / Q000517:prevention & control*; D010931:Plague Vaccine / Q000235:genetics / Q000276:immunology*; D013014:SOS Response, Genetics; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics* / Q000502:physiology; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014774:Virulence / Q000235:genetics; D015010:Yersinia pestis / Q000235:genetics / Q000472:pathogenicity*
D010931:Plague Vaccine; D014613:Vaccines, Attenuated; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific)