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Infection and Immunity, November 2001, p. 6725-6730, Vol. 69, No. 11
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.11.6725-6730.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Salmonella DNA Adenine Methylase Mutants Confer Cross-Protective Immunity

Douglas M. Heithoff,1 Elena Y. Enioutina,2 Raymond A. Daynes,2,3 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 931061; Department of Pathology, University of Utah, Salt Lake City, Utah 841322; and Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Salt Lake City, Utah 841123

Received 1 June 2001/Returned for modification 24 July 2001/Accepted 7 August 2001

Salmonella isolates that lack or overproduce DNA adenine methylase (Dam) elicited a cross-protective immune response to different Salmonella serovars. The protection afforded by the Salmonella enterica serovar Typhimurium Dam vaccine was greater than that elicited in mice that survived a virulent infection. S. enterica serovar Typhimurium Dam mutant strains exhibited enhanced sensitivity to mediators of innate immunity such as antimicrobial peptides, bile salts, and hydrogen peroxide. Also, S. enterica serovar Typhimurium Dam- vaccines were not immunosuppressive; unlike wild-type vaccines, they failed to induce increased nitric oxide levels and permitted a subsequent robust humoral response to diptheria toxoid antigen in infected mice. Dam mutant strains exhibited a low-grade persistence which, coupled with the nonimmunosuppression and the ectopic protein expression caused by altered levels of Dam, may provide an expanded source of potential antigens in vaccinated hosts.

* Corresponding author. Mailing address: Department 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, November 2001, p. 6725-6730, Vol. 69, No. 11
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.11.6725-6730.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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