Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Until now human pathogenic fungi were not known to possess such toxins. Here we identify the first fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signaling pathway and activates epithelial immunity. Toxin-mediated membrane permeabilization is enhanced by a positively charged C-terminus and triggers an inward current concomitant with calcium influx. C. albicans strains lacking this toxin do not activate or damage epithelial cells and are avirulent in animal models of mucosal infection. We propose the name ‘Candidalysin’ for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans.

The continued detection of zoonotic viral infections in bats has led to the microbial fauna of these mammals being studied at a greater level than ever before. Whilst numerous pathogens have been discovered in bat species, infection with lyssaviruses is of particular significance from a zoonotic perspective as, where human infection has been reported, it is invariably fatal. Here we review the detection of lyssaviruses within different bat species and overview what is understood regarding their maintenance and transmission following both experimental and natural infection. We discuss the relevance of these pathogens as zoonotic agents and the threat of newly discovered viruses to human populations.

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Microarray data reported elsewhere indicated that herpes simplex virus 1 induces the up-regulation of nuclear factor B (NF-B)-regulated genes, including that of its inhibitor, IB␣, consistent with the reports that wild-type virus induces the activation of NF-B. In this report we show that activation of NF-B in infected cells is linked to the activation of protein kinase R (PKR). Specifically: (i) PKR is activated in infected cells although the effects of the activated enzyme on protein synthesis are negated by the viral gene ␥134.5, which encodes a protein phosphatase 1␣ accessory factor that enables the dephosphorylation of the ␣ subunit of eukaryotic translation initiation factor 2. NF-B is activated in wild-type murine embryonic fibroblasts but not in related PKR-null cells. (ii) In cells infected with a replication-competent ⌬␥ 134.5 mutant (R5104), but carrying a U S11 gene expressed early in infection, eukaryotic translation initiation factor 2␣ is not phosphorylated, and in in vitro assays, PKR bound to the U S11 protein is not phosphorylated on subsequent addition of double-stranded RNA. Here we report that this mutant does not activate PKR, has no effect on the accumulation of IB␣, and does not cause the translocation of NF-B in infected cells. (iii) One hypothesis advanced for the activation of NF-B is that it blocks apoptosis induced by viral gene products. The replication-competent R5104 mutant does not induce the programmed cell's death. We conclude that in herpes simplex virus 1-infected cells, activation of NF-B depends on activation of PKR and that NF-B is not required to block apoptosis in productively infected cells.

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