Candida auris is an emerging worldwide concern, but comparative data about the virulence of different C. auris lineages in mammalian hosts is lacking. Different isolates of the four prevalent C. auris clades (South Asian n = 5, East Asian n = 4, South African n = 5, and South American n = 5) were compared to assess their virulence in a neutropenic murine bloodstream infection model with C. albicans as reference. C. auris, regardless of clade, proved to be less virulent than C. albicans. Highest overall mortality at day 21 was observed for the South American clade (96%), followed by the South Asian (80%), South African (45%) and East Asian (44%) clades. Fungal burden results showed close correlation with lethality. Histopathological examination revealed large aggregates of blastoconidia and budding yeast cells in the hearts, kidneys and livers but not in the spleens. The myocardium of apparently healthy sacrificed mice as well as of mice found moribund showed contraction band necrosis in case of all lineages. Regardless of clade, the heart and kidneys were the most heavily affected organs. Isolates of the same clade showed differences in virulence in mice, but a markedly higher virulence of the South American clade was clearly demonstrated.

The in vitro activity of caspofungin and micafungin was determined with and without farnesol in RPMI-1640 against Candida parapsilosis biofilms. Drug interactions were examined using the XTT colorimetric assay-based broth microdilution checkerboard method. Drug-drug interactions were assessed utilizing a fractional inhibitory concentration index (

The spreading of multidrug-resistant Candida auris is considered as an emerging global health threat. The number of effective therapeutic regimens is strongly limited; therefore, development of novel strategies is needed. Farnesol is a quorum-sensing molecule with a potential antifungal and/or adjuvant effect; it may be a promising candidate in alternative treatment against Candida species including C. auris. To examine the effect of farnesol on C. auris, we performed experiments focusing on growth, biofilm production ability, production of enzymes related to oxidative stress, triazole susceptibility and virulence. Concentrations ranging from 100 to 300 µM farnesol caused a significant growth inhibition against C. auris planktonic cells for 24 h (p < 0.01-0.05). Farnesol treatment showed a concentration dependent inhibition in terms of biofilm forming ability of C. auris; however, it did not inhibit significantly the biofilm development at 24 h. Nevertheless, the metabolic activity of adhered farnesol pre-exposed cells (75 µM) was significantly diminished at 24 h depending on farnesol treatment during biofilm formation (p < 0.001-0.05). Moreover, 300 µM farnesol exerted a marked decrease in metabolic activity against one-day-old biofilms between 2 and 24 h (p < 0.001). Farnesol increased the production of reactive species remarkably, as revealed by 2 ,7-dichlorofluorescein (DCF) assay {3.96 ± 0.89 [nmol DCF (OD 640) −1 ] and 23.54 ± 4.51 [nmol DCF (OD 640) −1 ] for untreated cells and farnesol exposed cells, respectively; p < 0.001}. This was in line with increased superoxide dismutase level {85.69 ± 5.42 [munit (mg protein) −1 ] and 170.11 ± 17.37 [munit (mg protein) −1 ] for untreated cells and farnesol exposed cells, respectively; p < 0.001}, but the catalase level remained statistically comparable between treated and untreated cells (p > 0.05). Concerning virulence-related enzymes, exposure to 75 µM farnesol did not influence phospholipase or aspartic proteinase activity (p > 0.05). The interaction between fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole and farnesol showed clear synergism (FICI ranges from 0.038 to 0.375) against one-day-old biofilms. Regarding in vivo experiments, daily 75 µM farnesol treatment decreased the

Candida auris biofilms exhibit decreased susceptibility to echinocandins, which is associated with poorer clinical outcomes. Farnesol is a quorum-sensing molecule enhancing the activity of antifungals; therefore, we evaluated the in vitro effect of farnesol with anidulafungin, caspofungin, or micafungin against biofilms using fractional inhibitory concentration indexes (FICI), Bliss independence model, LIVE/DEAD-assay and scanning electron microscopy. Based on mathematical models, farnesol caused synergism in eleven out of twelve cases (FICIs range 0.133-0.507; Bliss synergy volume range 70.39–204.6 μM2%). This was confirmed by microscope images of combination-exposed biofilms. Our study showed the prominent effect of farnesol with echinocandins against C. auris biofilms.

Summary Background Candidaemia is a common life‐threatening disease among hospitalised patients, but the effect of the Candida biofilm‐forming ability on the clinical outcome remains controversial. Objective The aim was to determine the impact of biofilms, specifically focusing on biofilm mass and metabolic activity, on the mortality in candidaemia. Patients/Methods The clinical data of patients (n = 127) treated at the University of Debrecen, Clinical Centre, between January 2013 and December 2018, were investigated retrospectively. Biofilm formation was assessed using the crystal violet and XTT assays, measuring the biofilm mass and metabolic activity, respectively. Isolates were classified as low, intermediate and high biofilm producers both regarding biofilm mass and metabolic activity. The susceptibility of one‐day‐old biofilms to fluconazole, amphotericin B, anidulafungin, caspofungin and micafungin was evaluated and compared to planktonic susceptibility. Results Intermediate/high biofilm mass was associated with significantly higher mortality (61%). All Candida tropicalis, Candida parapsilosis and Candida glabrata isolates originating from fatal infections were intermediate/high biofilm producers, whereas this ratio was 85% for Candida albicans. Solid malignancy was associated with intermediate/high biofilm producers (P = .043). The mortality was significantly higher in infections caused by Candida strains producing biofilms with intermediate/high metabolic activity (62% vs. 33%, P = .010). The ratio of concomitant bacteraemia was higher for isolates forming biofilms with low metabolic activity (53% vs 28%, P = .015). Conclusions This study provides evidence that the Candida biofilms especially with intermediate/high metabolic activity are related to higher mortality in candidaemia.