Capacity of ivanolysin O to replace listeriolysin O in phagosomal escape and in vivo survival of Listeria monocytogenes.
Listeriolysin O (LLO, hly-encoded) is a major virulence factor secreted by the pathogen Listeria monocytogenes. The amino acid sequence of LLO shows a high degree of similarity with that of ivanolysin O (ILO), the cytolysin secreted by the ruminant pathogen Listeria ivanovii. Here, it was tested whether ILO could functionally replace LLO by expressing the gene encoding ILO under the control of the hly promoter, in an hly-deleted strain of L. monocytogenes. It is shown that ILO allows efficient phagosomal escape of L. monocytogenes in both macrophages and hepatocytes. Moreover, expression of ILO is not cytotoxic and promotes normal intracellular multiplication. In vivo, the ILO-expressing strain can multiply and persist for several days in the liver of infected mice but is unable to survive in the spleen. This work underscores the key role played by the cytolysin in the virulence of pathogenic Listeria.
Frehel
Claude
C
Laboratoire de Microbiologie, INSERM U-570, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Lety
Marie-Annick
MA
Laboratoire de Microbiologie, INSERM U-570, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Autret
Nicolas
N
Laboratoire de Microbiologie, INSERM U-570, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Beretti
Jean-Luc
JL
Laboratoire de Microbiologie, INSERM U-570, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Berche
Patrick
P
Laboratoire de Microbiologie, INSERM U-570, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Charbit
Alain
A
Laboratoire de Microbiologie, INSERM U-570, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
D000818:Animals; D001427:Bacterial Toxins; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006460:Hemolysin Proteins; D006461:Hemolysis; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010588:Phagosomes / Q000382:microbiology*; D014407:Tumor Cells, Cultured; D014774:Virulence
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C038705:hlyA protein, Listeria monocytogenes