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Infection and Immunity, November 2004, p. 6707-6710, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6707-6710.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

LcrV Synthesis Is Altered by DNA Adenine Methylase Overproduction in Yersinia pseudotuberculosis and Is Required To Confer Immunity in Vaccinated Hosts

Golnaz Badie, Douglas M. Heithoff, and Michael J. Mahan*

Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California

Received 3 June 2004/ Returned for modification 14 July 2004/ Accepted 29 July 2004

Yersinia pseudotuberculosis mutants that overproduce the DNA adenine methylase (DamOP Yersinia) are attenuated, confer robust protective immune responses, and synthesize or secrete several Yersinia outer proteins (Yops) under conditions that are nonpermissive for synthesis and secretion in wild-type strains. To understand the molecular basis of immunity elicited by DamOP Yersinia, we investigated the effects of Dam overproduction on the synthesis and localization of a principal Yersinia immunogen, LcrV, a low-calcium-responsive virulence factor involved in Yop synthesis, localization, and suppression of host inflammatory activities. Dam overproduction relaxed the stringent temperature and calcium regulation of LcrV synthesis. Moreover, the LcrV-dependent synthesis and localization of the actin cytotoxin, YopE, were shown to be relaxed in DamOP cells, suggesting that the synthesis and localization of Yops can occur via both LcrV-dependent and -independent mechanisms. Last, the immunity conferred by DamOP Yersinia was strictly dependent on the presence of LcrV, which may result from its role (i) as an immunogen, (ii) as an immunomodulator of host anti-inflammatory activities, or (iii) in the altered synthesis and localization of Yops that could contribute to immunogen repertoire expansion.

* 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.lscf.ucsb.edu.

Editor: A. D. O'Brien

Infection and Immunity, November 2004, p. 6707-6710, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6707-6710.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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