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.