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Background The deep-seated infections caused by the Candida genus are associated with a high mortality rate, and Candida albicans is the most frequent species associated with these diseases. The fungal wall is composed of macromolecules not synthesized by the host, and therefore is a source of ligands recognized by innate immune cells. Methods We performed a comparative study analyzing the cell wall composition and organization of Candida tropicalis, Candida guilliermondii, Candida krusei, and Candida auris, along with their ability to stimulate cytokine production and phagocytosis by human innate immune cells. Results We found that the wall of these species had the basic components already described in C. albicans, with most of the chitin and b1,3-glucan located underneath the mannan layer. However, the walls of C. krusei and C. auris were rich in chitin and the former had a lower content of mannans. C. guilliermondii contained changes in the mannan and the b1,3-glucan levels. These species were differentially phagocytosed by human macrophages and stimulated cytokine production in a dectin-1-dependent pathway. C. krusei showed the most significant changes in the tested parameters, whereas C. auris behaved like C. albicans. Conclusion Our results suggest that the cell wall and innate immune recognition of C. tropicalis, C. guilliermondii, C. krusei, and Candida auris is different from that reported for C. albicans.

Background Sporothrix schenckii is a neglected fungal pathogen for the human being and other mammals. In several fungal systems, Och1 is a Golgi α1,6-mannosyltransferase with a key function in the synthesis of N-linked glycans; which are important elements during the host-fungus interplay. The role of OCH1 in fungal virulence seems to be species-specific, being an essential component for Candida albicans virulence and dispensable during the interaction of Aspergillus fumigatus with the host. Methods Here, we silenced S. schenckii OCH1 and characterized the phenotype of the mutant strains. Results The mutant strains did not show defects in the cell or colony morphology, the growth rate or the ability to undergo dimorphism; but the cell wall changed in both composition and exposure of inner components at the surface. When interacting with human monocytes, the silenced strains had a reduced ability to stimulate TNFα and IL-6 but stimulated higher levels of IL-10. The interaction with human macrophages was also altered, with reduced numbers of silenced cells phagocytosed. These strains showed virulence attenuation in both Galleria mellonella and in the mouse model of sporotrichosis. Nonetheless, the cytokine levels in infected organs did not vary significantly when compared with the wild-type strain. Conclusion Our data demonstrate that OCH1 silencing affects different aspects of the S. schenckii-host interaction.

Candida parapsilosis is an important, emerging opportunistic fungal pathogen. Highly mannosylated fungal cell wall proteins are initial contact points with host immune systems. In Candida albicans, Och1 is a Golgi 1,6-mannosyltransferase that plays a key role in the elaboration of the N-linked mannan outer chain. Here, we disrupted C. parapsilosis OCH1 to gain insights into the contribution of N-linked mannosylation to cell fitness and to interactions with immune cells. Loss of Och1 in C. parapsilosis resulted in cellular aggregation, failure of morphogenesis, enhanced susceptibility to cell wall perturbing agents and defects in wall composition. We removed the cell wall O-linked mannans by -elimination, and assessed the relevance of mannans during interaction with human monocytes. Results indicated that O-linked mannans are important for IL-1 stimulation in a dectin-1 and TLR4-dependent pathway; whereas both, N- and O-linked mannans are equally important ligands for TNF and IL-6 stimulation, but neither is involved in IL-10 production. Furthermore, mice infected with C. parapsilosis och1 null mutant cells had significantly lower fungal burdens compared to wild-type (WT)-challenged counterparts. Therefore, our data are the first to demonstrate that C. parapsilosis N- and O-linked mannans have different roles in host interactions than those reported for C. albicans.