14CONFAP Stress responses and virulence in fungal pathogens endemic to Brazil

The ability of fungal pathogens to survive the armoury of defences employed by the human immune system is vital for such pathogens to cause life-threatening infections. These defences include the production of highly toxic oxidants which damage all of the main components of the fungal cell leading to cell death. The laboratory headed by Professor Jan Quinn has extensive experience in studying how certain fungal pathogens mount responses to these oxidants, to allow the pathogens to evade immune-cell killing mechanisms. In particular the Quinn lab have studied stress responses in the major human fungal pathogen, Candida albicans, which has provided much insight into stress adaptation of this fungal pathogen to the host environment. In contrast, much less is known about stress response mechanisms in fungi belonging to the Sporothrix schenckii complex, which are the causative agent of sporotrichosis - a prevalent frequent fungal disease in Latin America. Two such fungi, S. schenckii sensu stricto and S. brasiliensis have been associated with endemic areas in Brazil. It is likely that such pathogens need to mount robust stress responses to survive host defences, and the overall goal of this research partnership is to facilitate a molecular study of stress responses in the emerging pathogens S. schenckii sensu stricto and S. brasiliensis.

The ability of fungal pathogens to survive immune defence mechanisms employed by phagocytic cells is imperative for such pathogens to cause life-threatening systemic infections. Innate immune cells employ an armoury of different chemical weapons to destroy the pathogen including toxic reactive oxygen species (ROS), cationic fluxes, acidification of the phagosome, and the production of anti-microbial peptides. The Quinn lab is internationally recognised for their work on stress responses and virulence in the fungal pathogen Candida albicans, which has provided novel insight into stress adaptation of this fungal pathogen to the host environment. In contrast, much less is known about stress response mechanisms in fungi belonging to the Sporothrix schenckii complex, which are the causative agent of sporotrichosis - the most frequent subcutaneous mycosis in Latin America. Two such fungi, S. schenckii sensu stricto and S. brasiliensis have been associated with endemic areas in Brazil. It is likely that such pathogens need to mount robust stress responses to survive host defences as phagocytosis of S. schenckii sensu stricto by macrophages triggers the oxidative burst resulting in high levels of ROS. Recently, the genomes of both S. schenckii and S. brasiliensis have been sequenced and annotated (by the groups of Professor Maria Sueli Soares Felipe in collaboration with the Lopes-Bezerra group). This allowed for an in silico analysis which revealed the conservation of many but not all key stress regulators, and interesting sequence differences in conserved regulators such as the predicted Hog1 stress activated protein kinase in S. brasiliensis. The overall goal of this research partnership is to facilitate a molecular study of stress responses in the emerging pathogens S. schenckii sensu stricto and S. brasiliensis.

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