Melanin of Sporothrix globosa affects the function of THP-1 macrophages and modulates the expression of TLR2 and TLR4

CRISPR-based tools for genetic manipulation in pathogenicSporothrixspecies

“…In this respect, it has been shown that DHN-melanin from Aspergillus fumigatus disrupts the phagosomal recruitment of Ca 2+ /calmodulin-dependent protein kinase and the autophagy pathway LC3-associated phagocytosis preventing the elimination of conidia (Akoumianaki et al ., 2016; Goncalves et al, 2020). Previous studies have shown that S. schenckii and S. globosa UV-induced mutants deficient for DHN-melanin production are more susceptible to oxidative/nitrosative stresses and induce higher levels of reactive oxygen species by human monocytes and murine macrophages (Guan et al ., 2021; Romero-Martinez et al ., 2000). Furthermore, a S. globosa DHN-melanin deficient strain is less resistant to phagocytosis (Guan et al ., 2021; Masternak et al ., 2000).…”

“…Previous studies have shown that S. schenckii and S. globosa UV-induced mutants deficient for DHN-melanin production are more susceptible to oxidative/nitrosative stresses and induce higher levels of reactive oxygen species by human monocytes and murine macrophages (Guan et al ., 2021; Romero-Martinez et al ., 2000). Furthermore, a S. globosa DHN-melanin deficient strain is less resistant to phagocytosis (Guan et al ., 2021; Masternak et al ., 2000). Therefore, the sensitivity of pks1 mutants to H 2 O 2 and tBOOH observed in this study was consistent with the view that pigments like DHN-melanin protect Sporothrix against oxidative stress.…”

“…UV-induced DHN-melanin deficient strains of S. schenckii were less resistant to oxidative/nitrosative stresses and phagocytosis by human monocytes or murine macrophages (Romero-Martinez et al, 2000). Conidia from a wild-type (WT) Sporothrix globosa strain revealed a lower expression of MHC class II in murine macrophages and a higher fungal burden in spleen when compared to an UV-induced albino mutant (Guan et al, 2021; Masternak et al, 2000; Song et al, 2021). In addition, DHN-melanin inhibitors enhanced the in vitro susceptibility of S. brasiliensis and S. schenckii to the antifungal drug terbinafine.…”

Virulence Factors of Sporothrix schenckii

“…As an antifungal resistance factor, melanin and its synthesis pathways could be a target for the design of new antifungal drugs for sporotrichosis therapies. A recent study has shown that melanin is a key factor to prevent phagocytosis of S. globosa by THP-1 macrophages, given that this cell wall component neutralizes the respiratory burst and suppresses the ROS and NO production; besides, the presence of melanin in S. globosa decreases the expression of TLR2 and TLR4, receptors involved in the recognition of the fungus [ 74 , 75 , 76 ]. Therefore, the presence of a said component in the cell wall of the pathogen reduces the possibility of the host to fight the fungus.…”

“…Therefore, the presence of a said component in the cell wall of the pathogen reduces the possibility of the host to fight the fungus. Finally, the pro-inflammatory response is also decreased, especially TNFα and IL-6, in the presence of S. schenckii wild-type fungus compared to the mutant lacking melanin [ 74 ].…”