Percorrer por autor "Brown, Alistair J."
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- Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetatePublication . Mota, Sandra; Alves, Rosana; Carneiro, Catarina; Silva, Sónia; Brown, Alistair J.; Istel, Fabian; Kuchler, Karl; Sampaio, Paula; Casal, Margarida; Henriques, Mariana; Paiva, SandraCandida glabrata is considered a major opportunistic fungal pathogen of humans. The capacity of this yeast species to cause infections is dependent on the ability to grow within the human host environment and to assimilate the carbon sources available. Previous studies have suggested that C. albicans can encounter glucose-poor microenvironments during infection and that the ability to use alternative non-fermentable carbon sources, such as carboxylic acids, contributes to the virulence of this fungus. Transcriptional studies on C. glabrata cells identified a similar response, upon nutrient deprivation. In this work, we aimed at analyzing biofilm formation, antifungal drug resistance, and phagocytosis of C. glabrata cells grown in the presence of acetic acid as an alternative carbon source. C. glabrata planktonic cells grown in media containing acetic acid were more susceptible to fluconazole and were better phagocytosed and killed by macrophages than when compared to media lacking acetic acid. Growth in acetic acid also affected the ability of C. glabrata to form biofilms. The genes ADY2a, ADY2b, FPS1, FPS2, and ATO3, encoding putative carboxylate transporters, were upregulated in C. glabrata planktonic and biofilm cells in the presence of acetic acid. Phagocytosis assays with fps1 and ady2a mutant strains suggested a potential role of FPS1 and ADY2a in the phagocytosis process. These results highlight how acidic pH niches, associated with the presence of acetic acid, can impact in the treatment of C. glabrata infections, in particular in vaginal candidiasis.
- Lactic acid increases the susceptibility of Candida albicans to fluconazolePublication . Alves, Rosana; Mota, Sandra; Silva, Sónia; Rodrigues, Célia; Brown, Alistair J.; Henriques, Mariana; Casal, Margarida; Paiva, SandraCandida spp. often inhabit niches that are glucose-limited but rich in alternative carbon sources, such as lactate or acetate, an ability that contributes to cells’ virulence. In glucose-poor niches, Candida albicans cells express JEN1 and JEN2 genes encoding the carboxylic acids transporters Jen1 and Jen2, respectively, which have been reported to be important in the early stages of infection. In this work, we aimed at analysing biofilm formation and antifungal drug resistance of C. albicans cells grown either in the presence of glucose or lactic acid. Additionally, we tested the involvement of Jen1 and Jen2 on these processes. Our results show that biofilm formation and susceptibility to fluconazole depend on the carbon source used. Wild-type and jen1jen2 lactic acid-grown cells formed more biofilm biomass, with predominance of yeast cells, than the ones grown in glucose. In the presence of this sugar a hyphae network is observed only for wild-type cells. In the presence of lactic acid, a jen1jen2 mutant strain exhibited a more compact biofilm with higher resistance to fluconazole when compared to the wild type. In the case of planktonic cells, the phenotype was exactly the opposite; the double mutant strain was more susceptible to fluconazole in lactic acid containing media. These findings show that carboxylic acids transporters have an important role in biofilm formation and in the acquisition of resistance to antifungal drugs, supporting the view that adaptation of Candida cells to the carbon source present in host niches affects their pathogenicity.