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Infection and Immunity, December 2001, p. 7610-7615, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7610-7615.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

DNA Adenine Methylase Is Essential for Viability and Plays a Role in the Pathogenesis of Yersinia pseudotuberculosis and Vibrio cholerae

Steven M. Julio,1 Douglas M. Heithoff,1 Daniele Provenzano,2 Karl E. Klose,2 Robert L. Sinsheimer,1 David A. Low,1 and Michael J. Mahan1,*

Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106,1 and Department of Microbiology, University of Texas Health Science Center, San Antonio, Texas 78229-39002

Received 7 June 2001/Returned for modification 20 August 2001/Accepted 6 September 2001

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.

* Corresponding author. Mailing address: Dept. of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA 93106. Phone: (805) 893-7160. Fax: (805) 893-4724. E-mail: mahan{at}lifesci.ucsb.edu.

Infection and Immunity, December 2001, p. 7610-7615, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7610-7615.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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