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001-es BibID:	BIBFORM085057
035-os BibID:	(cikkazonosító)957 (WOS)000539331800001 (Scopus)85085883554
Első szerző:	Nagy Fruzsina (molekuláris biológus)
Cím:	In vitro and in vivo effect of exogenous farnesol exposure against Candida auris / Fruzsina Nagy, Eszter Vitális, Ágnes Jakab, Andrew M. Borman, Lajos Forgács, Zoltán Tóth, László Majoros, Renátó Kovács
Dátum:	2020
ISSN:	1664-302X
Megjegyzések:	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 uM farnesol caused a significant growth inhibition against C. auris planktonic cells for 24 hours (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 hours. Nevertheless, the metabolic activity of adhered farnesol pre-exposed cells (75 uM) was significantly diminished at 24 hours depending on farnesol treatment during biofilm formation (p<0.001-0.05). Moreover, 300 uM farnesol exerted a marked decrease in metabolic activity against one-day-old biofilms between 2 and 24 hours (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 (OD640)-1] and 23.54?4.51 [nmol DCF (OD640)-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 uM farnesol did not influence phospholipase or aspartic proteinase activity (p>0.05). The interaction between fluconazole, intraconazole, 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 uM farnesol treatment decreased the fungal burden in an immuncompromised murine model of disseminated candidiasis, especially in case of inocula pre-exposed to farnesol (p<0.01). In summary, farnesol shows a promising therapeutic or adjuvant potential in traditional or alternative therapies such as catheter lock therapy.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Frontiers in Microbiology. - 11 (2020), p. 1-12. -
További szerzők:	Vitális Eszter (1977-) (orvos) Jakab Ágnes (1987-) (biológus) Borman, Andrew M. Forgács Lajos Tóth Zoltán (1990-) (molekuláris biológus) Majoros László (1966-) (szakorvos, klinikai mikrobiológus) Kovács Renátó László (1987-) (molekuláris biológus)
Pályázati támogatás:	EFOP-3.6.3-VEKOP-16-2017-00009 EFOP ÚNKP-19-3 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM082894
Első szerző:	Vitális Eszter (orvos)
Cím:	Candida biofilm production is associated with higher mortality in patients with candidaemia / Vitális Eszter, Nagy Fruzsina, Tóth Zoltán, Forgács Lajos, Bozó Aliz, Kardos Gábor, Majoros László, Kovács Renátó
Dátum:	2020
ISSN:	0933-7407
Megjegyzések:	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=0.043). The mortality was significantly higher in infections caused by Candida strains producing biofilms with intermediate/high metabolic activity (62% vs. 33%, p=0.010). The ratio of concomitant bacteraemia was higher for isolates forming biofilms with low metabolic activity (53% vs. 28%, p=0.015). Conclusions: This study provides evidence that the Candida biofilms especially with intermediate/high metabolic activity are related to higher mortality in candidemia.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Mycoses. - 63 : 4 (2020), p. 352-360. -
További szerzők:	Nagy Fruzsina (1991-) (molekuláris biológus) Tóth Zoltán (1990-) (molekuláris biológus) Forgács Lajos Bozó Aliz (1984-) (biológus) Kardos Gábor (1974-) (szakorvos, klinikai mikrobiológus) Majoros László (1966-) (szakorvos, klinikai mikrobiológus) Kovács Renátó László (1987-) (molekuláris biológus)
Pályázati támogatás:	EFOP-3.6.3-VEKOP-16-2017-00009 EFOP Únkp-19-3 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Saját polcon: