Abstract
BackgroundParacoccidioides spp is a fungi genus and the agent of paracoccidioidomycosis. The strategies of infection used by these pathogens involve the expression of proteins related to adaptation to the host, particularly regarding the uptake of micronutrients. This study analyzed the adhesion of Paracoccidioides lutzii during conditions of copper (Cu) and iron (Fe) deprivation, while also evaluating the proteins expressed in conditions of Cu depletion in the presence of four extracellular matrix (ECM) components (laminin, fibronectin and types I and IV collagen).ResultsWe cultured the P. lutzii in a chemically defined media without Cu and Fe. The fungus was then placed in contact with different ECM components and adhesion was evaluated. A significant increase in binding to all ECM components was observed when the fungus was cultured without Cu; which might be related to some adhesins expression. A proteomic assay was developed and revealed 39 proteins expressed that are involved in processes such as virulence, protein synthesis, metabolism, energy, transcription, transport, stress response and the cell cycle when the fungus was interacting with the ECM components. The up-regulated expression of two important adhesins, enolase and 14-3-3, was observed at the fungal cell wall during the interaction with the ECM components, indicating the role of these proteins in the Paracoccidioides–host interaction.ConclusionsThis study is important for determining prospective proteins that may be involved in the interaction of Paracoccidioides with a host. Understanding the adaptive response to different growth conditions, elucidating the processes of adhesion and cell invasion, and identifying the proteins that are differentially expressed during the fungus-host interaction may help elucidate mechanisms used for survival and growth of Paracoccidioides in various human tissues.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-014-0302-7) contains supplementary material, which is available to authorized users.
Highlights
Paracoccidioides spp is a fungi genus and the agent of paracoccidioidomycosis
Adhesion of Paracoccidioides lutzii to extracellular matrix (ECM) components during Cu and Fe depletion Following incubation in MVM without Cu (MVM-W-Cu medium), the P. lutzii yeast phase presented a significant increase (p < 0.05) in adhesion (Figure 1) in the presence of all tested ECM components, while in MVM without Fe (MVM-W-Fe), we observed a significant decrease
Cu depletion led to increased expression of the main adhesins, except for gp43 and malate synthase (MLT), whereas Fe depletion led to decreased expression in all studied adhesins
Summary
Paracoccidioides spp is a fungi genus and the agent of paracoccidioidomycosis. The strategies of infection used by these pathogens involve the expression of proteins related to adaptation to the host, regarding the uptake of micronutrients. Cu serves as a catalytic and structural cofactor for enzymes involved many processes, including energy generation, Fe acquisition, oxygen transport and cellular metabolism [9]. Both the host and fungi have developed sophisticated strategies for acquiring the metals, even under conditions of limited availability. Several homeostatic mechanisms have been demonstrated in fungi, guaranteeing the maintenance of sufficient concentrations of Cu for cell growth without causing damage Posttranslational mechanisms, such as the intracellular trafficking of Cu transporters, have been identified in mammals. Cu homeostasis is mediated by the transcriptional regulation of genes involved in Cu acquisition, mobilization, and sequestration [10,11]
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