Exfoliative toxin e, a new Staphylococcus aureusvirulence factor with host-specific activity

Imanishi, Ichiro; Barbosa Caetano, Ana-Carolina; De Paula Castro, Luiz; ROCHA TARTAGLIA, Natayme; Mariutti, Ricardo; Guedon, Eric; Even, Sergine; Berkova, Nadia; Arni, Raghuvir,; Seyffert, Nubia; Azevedo, Vasco; Nishifuji, Koji; Le Loir, Yves

Exfoliative toxin e, a new Staphylococcus aureusvirulence factor with host-specific activity

2019

Exfoliative toxins (ETs) are secreted virulence factors produced by staphylococci. These serine proteasesspecifically cleave desmoglein 1 (Dsg1) in mammals and are key elements in staphylococcal skininfections. We recently identified a new et gene in S. aureus O46, a strain isolated from ovine mastitis.In the present study, we characterized the new et gene at a genetic level and the enzymatic activity ofthe deduced protein. The S. aureus O46 genome was re-assembled, annotated and compared with otherpublicly available S. aureus genomes. The deduced amino acid sequence of the new et gene shared 40%,53% and 59% sequence identity to those of ETA, ETB and ETD, respectively. The new et gene sharedthe same genetic vicinity and was similar in other S. aureus strains bearing this gene. The recombinantenzyme of the new et gene caused skin exfoliation in vivo in neonatal mice. The new et-gene wasthus named ete, encoding a new type (type E) of exfoliative toxin. We showed that ETE degraded theextracellular segments of Dsg1 in murine, ovine and caprine epidermis, as well as in ovine teat canalepithelia, but not that in bovine epidermis. We further showed that it directly hydrolyzed human andswine Dsg1 as well as murine Dsg1α and Dsg1β, but not canine Dsg1 or murine Dsg1γ. Molecularmodeling revealed a correlation between the preferred orientation of ETE docking on its Dsg1 cleavagesite and species-specific cleavage activity, suggesting that the docking step preceding cleavageaccounts for the ETE species-specificity. This new virulence factor may contribute to the bacterialcolonization on the stratified epithelia in certain ruminants with mastitis.

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