Fonsecaea pedrosoi response to zinc deprivation

Fungal diseases significantly impact human mortality and morbidity. However, despite the number of annual deaths caused by fungi exceeding 1.6 million, these microorganisms are often neglected. Fonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), a chronic mycosis that affects the skin and subcutaneous tissue that, in 2017, was included in the WHO list of neglected tropical diseases. It is essentially an occupational disease that affects individuals in poverty, causing significant morbidity and mortality. CBM is a disease of global distribution, and most cases are described in tropical and subtropical regions of America, Africa and Asia. Despite its importance in the etiology of the disease, the molecular mechanisms involved in the interaction of F. pedrosoi with the host are still poorly explored. During the infectious process, the host limits the availability of zinc to fungal pathogens in order to contain the infection, a process called nutritional immunity. In this work, we show that F. pedrosoi is able to grow in a wide range of zinc concentration and that genes related to zinc uptake are induced in zinc-limiting conditions. Proteomic analysis revealed that after 48 h of exposure to zinc scarcity synthesis of fatty acid and the pentose-phosphate pathway are up-regulated. On the other hand, protein synthesis is repressed. Additionally, glucan increases while chitin content is reduced in the cell wall under zinc limitation, demonstrating that cell wall remodeling is important for adaptation to this stress condition.