Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Mycobacterium bovis Bacille Calmette-Guerin Strains Secreting Listeriolysin of Listeria monocytogenes

Jurgen Hess, Diana Miko, Andre Catic, Vera Lehmensiek, David G. Russell and Stefan H. E. Kaufmann
Proceedings of the National Academy of Sciences of the United States of America
Vol. 95, No. 9 (Apr. 28, 1998), pp. 5299-5304
Stable URL: http://www.jstor.org/stable/44708
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Mycobacterium bovis Bacille Calmette-Guerin Strains Secreting Listeriolysin of Listeria monocytogenes
Preview not available

Abstract

Recombinant (r) Mycobacterium bovis strains were constructed that secrete biologically active listeriolysin (Hly) fusion protein of Listeria monocytogenes. The r-BCG strains pAT261:Hly or pMV306:Hly expressed plasmid multicopies or chromosomal single copies of the hly gene, respectively. Human and murine macrophage-like cell lines were infected with r-BCG pAT261:Hly and pMV306:Hly strains. Interestingly, intracellular persistence of both r-BCG strains was reduced in macrophages as compared with the parental BCG strain. By immunogold labeling Hly was detected in membrane structures and within the phagosomal space of macrophages. In addition, Hly was localized within cytoplasmic vacuoles outside the mycobacteria-containing phagosome of host cells infected with r-BCG pAT261:Hly or r-BCG pMV306:Hly. Hly fusions consistently colocalized with a lysosome-associated membrane glycoprotein, suggesting that membrane-attack conformation of Hly was not altered. Although r-BCG pAT261:Hly and r-BCG pMV306:Hly microorganims apparently did not egress into the cytoplasmic compartment of host cells, they both improved major histocompatibility complex class I presentation of cophagocytosed soluble protein as compared with wild-type BCG microbes. These data suggest that Hly secretion endows BCG with an improved capacity to stimulate CD8 T cells. Because CD8 T cells play a major role in protection against tuberculosis such Hly secreting r-BCG constructs are antituberculosis vaccine candidates.

Page Thumbnails

  • Thumbnail: Page 
5299
    5299
  • Thumbnail: Page 
5300
    5300
  • Thumbnail: Page 
5301
    5301
  • Thumbnail: Page 
5302
    5302
  • Thumbnail: Page 
5303
    5303
  • Thumbnail: Page 
5304
    5304