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Infection and Immunity, October 2009, p. 4371-4382, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00419-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Recombinant Listeria monocytogenes Expressing a Cell Wall-Associated Listeriolysin O Is Weakly Virulent but Immunogenic{triangledown}

Javier A. Carrero, Boris Calderon, Hector Vivanco-Cid, and Emil R. Unanue*

Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, Missouri 63110

Received 15 April 2009/ Returned for modification 25 May 2009/ Accepted 4 August 2009

Listeriolysin O (LLO) is an essential virulence factor for the gram-positive bacterium Listeria monocytogenes. Our goal was to determine if altering the topology of LLO would alter the virulence and toxicity of L. monocytogenes in vivo. A recombinant strain was generated that expressed a surface-associated LLO (sLLO) variant secreted at 40-fold-lower levels than the wild type. In culture, the sLLO strain grew in macrophages, translocated to the cytosol, and induced cell death. However, the sLLO strain showed decreased infectivity, reduced lymphocyte apoptosis, and decreased virulence despite a normal in vitro phenotype. Thus, the topology of LLO in L. monocytogenes was a factor in the pathogenesis of the infection and points to a role of LLO secretion during in vivo infection. The sLLO strain was cleared by severe combined immunodeficient (SCID) mice. Despite the attenuation of virulence, the sLLO strain was immunogenic and capable of eliciting protective T-cell responses.

* Corresponding author. Mailing address: Emil R. Unanue, Washington University School of Medicine, Department of Pathology and Immunology, 660 South Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-7440. Fax: (314) 362-1403. E-mail: unanue{at}pathology.wustl.edu

{triangledown} Published ahead of print on 10 August 2009.

Editor: J. L. Flynn

Infection and Immunity, October 2009, p. 4371-4382, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00419-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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