Peroxide sensing and signaling in the Sporothrix schenckii complex: an in silico analysis to uncover putative mechanisms regulating the Hog1 and AP-1 like signaling pathways.

In order to understand how fungal pathogens can survive inside the host, we must analyze how they evade the fungicidal mechanisms mounted by the host's immune system, such as generation of toxic reactive oxygen species. Studies have shown that infections caused by Sporothrix brasiliensis can be more aggressive than those due to Sporothrix schenckii. Therefore, we propose to analyze and compare the ability of these two pathogenic species to counteract oxidative stress, which, as noted, can be relevant in the host response to infection. We have shown that S. brasiliensis is more resistant to different oxidants, such as H2O2 and menadione, when compared with S. schenckii. Furthermore, our results suggest that the molecular mechanisms by which Sporothrix spp. AP-1 like transcription factors are regulated probably differs from the one seen in other fungal pathogens. Interestingly, comparison between sequences of SbHog1 and SsHog1 stress activated protein kinases suggest that S. brasiliensis Hog1 display mutations that could account for the differences seen in stress sensitivities of these two species. In summary, this is the first study to our knowledge to investigate oxidative stress responses of Sporothrix spp. and provided a model that can be employed in vivo to address how these fungal pathogens can surmount the oxidative stress generated by the host.