DNA adenine methylase is essential for viability and plays a role in the pathogenesis of Yersinia pseudotuberculosis and Vibrio cholerae.
Salmonella strains that lack or overproduce DNA adenine methylase (Dam) elicit a protective immune response to different Salmonella species. To generate vaccines against other bacterial pathogens, the dam genes of Yersinia pseudotuberculosis and Vibrio cholerae were disrupted but found to be essential for viability. Overproduction of Dam significantly attenuated the virulence of these two pathogens, leading to, in Yersinia, the ectopic secretion of virulence proteins (Yersinia outer proteins) and a fully protective immune response in vaccinated hosts. Dysregulation of Dam activity may provide a means for the development of vaccines against varied bacterial pathogens.
Julio
S M
SM
Department of Molecular, University of California, Santa Barbara, California 93106, USA.
Heithoff
D M
DM
Provenzano
D
D
Klose
K E
KE
Sinsheimer
R L
RL
Low
D A
DA
Mahan
M J
MJ
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001428:Bacterial Vaccines / Q000235:genetics / Q000627:therapeutic use*; D002771:Cholera / Q000517:prevention & control; D022121:Cholera Vaccines / Q000235:genetics / Q000627:therapeutic use; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000096:biosynthesis; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000096:biosynthesis / Q000235:genetics*; D014734:Vibrio cholerae / Q000472:pathogenicity* / Q000502:physiology; D015011:Yersinia pseudotuberculosis / Q000472:pathogenicity* / Q000502:physiology; D015012:Yersinia pseudotuberculosis Infections / Q000517:prevention & control
D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D022121:Cholera Vaccines; D011994:Recombinant Proteins; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific)