Recombinant Listeria monocytogenes expressing a cell wall-associated listeriolysin O is weakly virulent but immunogenic.
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.
Carrero
Javier A
JA
Washington University School of Medicine, Department of Pathology and Immunology, 660 South Euclid Ave., St. Louis, MO 63110, USA.
Calderon
Boris
B
Vivanco-Cid
Hector
H
Unanue
Emil R
ER
D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D006460:Hemolysin Proteins / Q000235:genetics / Q000276:immunology*; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D008099:Liver / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014774:Virulence
D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D016207:Cytokines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D014613:Vaccines, Attenuated; C038705:hlyA protein, Listeria monocytogenes