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001-es BibID:	BIBFORM113783
035-os BibID:	(cikkazonosító)81 (scopus)85167458717 (wos)001039695500001
Első szerző:	Balla Noémi (mikrobiológus)
Cím:	Total transcriptome analysis of Candida auris planktonic cells exposed to tyrosol / Balla Noémi, Jakab Ágnes, Kovács Fruzsina, Ragyák Ágota, Tóth Zoltán, Balázsi Dávid, Forgács Lajos, Bozó Aliz, Al Refai Farah, Borman Andrew M., Majoros László, Kovács Renátó
Dátum:	2023
ISSN:	2191-0855
Megjegyzések:	Tyrosol, a secondary metabolite of Candida species, regulates fungal morphogenesis, and its application may represent a novel innovative therapy against emerging multi-resistant fungal superbug such as Candida auris. In the current study, the effects of tyrosol on growth, redox homeostasis, intracellular microelement contents and activities of virulence-related enzymes released by C. auris were examined. To gain further information about the effect of tyrosol exposure, we revealed gene transcriptional changes using total transcriptome sequencing (RNA-Seq). At a concentration of 15 mM, tyrosol significantly decrease the growth of fungal cells within 2 h of its addition (5.6?107?1.2?107 and 2.5?107?0.6?107 colony forming unit/mL for control and tyrosol-treated cells, respectively). Furthermore, it enhanced the release of reactive oxygen species as confirmed by a dichlorofluorescein (DCF) assay (7.3?1.8 [nmol DCF (OD640)?1] versus 16.8?3.9 [nmol DCF (OD640)?1]), which was coincided with elevated superoxide dismutase, catalase and glutathione peroxidase activities. Tyrosol exerted in a 37%, 25%, 34% and 55% decrease in intracellular manganese, iron, zinc and copper contents, respectively, compared to control cells. The tyrosol treatment led to a 142 and 108 differentially transcripted genes with at least a 1.5-fold increase or decrease in transcription, respectively. Genes related to iron and fatty acid metabolism as well as nucleic acid synthesis were down-regulated, whereas those related to the antioxidative defence, adhesion and oxoacid metabolic processes were up-regulated. This study shows that tyrosol significantly influences growth, intracellular physiological processes and gene transcription in C. auris, which could highly support the development of novel treatment approaches against this important pathogen.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	AMB Express. - 13 : 1 (2023), p. 1-10. -
További szerzők:	Jakab Ágnes (1987-) (biológus) Kovács Fruzsina (2000-) (molekuláris biológus, biotechnológus) Ragyák Ágota Tóth Zoltán (1990-) (molekuláris biológus) Balázsi Dávid Forgács Lajos Bozó Aliz (1984-) (biológus) Al Refai, Farah Borman, Andrew M. Majoros László (1966-) (szakorvos, klinikai mikrobiológus) Kovács Renátó László (1987-) (molekuláris biológus)
Pályázati támogatás:	NKFIH FK138462 OTKA UNKP-22-5-DE-417 Egyéb BO/00127/21/8 MTA
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001-es BibID:	BIBFORM094600
035-os BibID:	(WoS)000709571800009 (Scopus)85117395605
Első szerző:	Nagy Fruzsina (molekuláris biológus)
Cím:	In vitro and in vivo interaction of caspofungin with isavuconazole against Candida auris planktonic cells and biofilms / Nagy Fruzsina, Tóth Zoltán, Nyikos Fanni, Forgács Lajos, Jakab Ágnes, Borman Andrew M., Majoros László, Kovács Renátó
Dátum:	2021
ISSN:	1369-3786
Megjegyzések:	The in vitro and in vivo efficacy of caspofungin was determined in combination with isavuconazole against Candida auris. Drug-drug interactions were assessed utilising the fractional inhibitory concentration indices (FICIs), the Bliss independence model and an immunocompromised mouse model. Median planktonic minimum inhibitory concentrations (pMICs) of 23 C. auris isolates were between 0.5 and 2 mg/L and between 0.015 and 4 mg/L for caspofungin and isavuconazole, respectively. Median pMICs for caspofungin and isavuconazole in combination showed 2-128-fold and 2-256-fold decreases, respectively. Caspofungin and isavuconazole showed synergism in 14 out of 23 planktonic isolates (FICI range 0.03-0.5; Bliss cumulative synergy volume range 0-4.83). Median sessile MICs (sMIC) of 14 biofilm-forming isolates were between 32 and > 32 mg/L and between 0.5 and > 2 mg/L for caspofungin and isavuconazole, respectively. Median sMICs for caspofungin and isavuconazole in combination showed 0-128-fold and 0-512-fold decreases, respectively. Caspofungin and isavuconazole showed synergistic interaction in 12 out of 14 sessile isolates (FICI range 0.023-0.5; Bliss cumulative synergy volume range 0.13-234.32). In line with the in vitro findings, synergistic interactions were confirmed by in vivo experiments. The fungal kidney burden decreases were more than 3 log volumes in mice treated with combination of 1 mg/kg caspofungin and 20 mg/kg isavuconazole daily; this difference was statistically significant compared with control mice (p < 0.001). Despite the favourable effect of isavuconazole in combination with caspofungin, further studies are needed to confirm the therapeutic advantage of this combination when treating an infection caused by C. auris.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Medical Mycology. - 59 : 10 (2021), p. 1015-1023. -
További szerzők:	Tóth Zoltán (1990-) (molekuláris biológus) Nyikos Fanni Forgács Lajos Jakab Ágnes (1987-) (biológus) Borman, Andrew M. Majoros László (1966-) (szakorvos, klinikai mikrobiológus) Kovács Renátó László (1987-) (molekuláris biológus)
Pályázati támogatás:	EFOP-3.6.3-VEKOP-16-2017-00009 EFOP GINOP-2.3.4-15-2020-00008 GINOP ÚNKP-19-3 Egyéb ÚNKP-20-3 Egyéb
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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
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