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1.

001-es BibID:BIBFORM072749
Első szerző:Fidler Gábor (molekuláris biológus, genetikus)
Cím:DNA Barcoding Coupled with High Resolution Melting Analysis Enables Rapid and Accurate Distinction of Aspergillus species / Fidler Gabor, Kocsube Sandor, Leiter Eva, Biro Sandor, Paholcsek Melinda
Dátum:2017
ISSN:1369-3786
Megjegyzések:We describe a high-resolution melting (HRM) analysis method that is rapid, reproducible, and able to identify reference strains and further 40 clinical isolates of Aspergillus fumigatus (14), A. lentulus (3), A. terreus (7), A. flavus (8), A. niger (2), A. welwitschiae (4), and A. tubingensis (2). Asp1 and Asp2 primer sets were designed to amplify partial sequences of the Aspergillus benA (beta-tubulin) genes in a closed-, single-tube system. Human placenta DNA, further Aspergillus (3), Candida (9), Fusarium (6), and Scedosporium (2) nucleic acids from type strains and clinical isolates were also included in this study to evaluate cross reactivity with other relevant pathogens causing invasive fungal infections. The barcoding capacity of this method proved to be 100% providing distinctive binomial scores; 14, 34, 36, 35, 25, 15, 26 when tested among species, while the within-species distinction capacity of the assay proved to be 0% based on the aligned thermodynamic profiles of the Asp1, Asp2 melting clusters allowing accurate species delimitation of all tested clinical isolates. The identification limit of this HRM assay was also estimated on Aspergillus reference gDNA panels where it proved to be 10?102 genomic equivalents (GE) except the A. fumigatus panel where it was 103 only. Furthermore, misidentification was not detected with human genomic DNA or with Candida, Fusarium, and Scedosporium strains. Our DNA barcoding assay introduced here provides results within a few hours, and it may possess further diagnostic utility when analyzing standard cultures supporting adequate therapeutic decisions.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
molecular barcoding
high resolution melting
Aspergillus
species level identification
standard cultures
Megjelenés:Medical Mycology. - 55 (2017), p. 642-659. -
További szerzők:Kocsubé Sándor Leiter Éva (1976-) (biológus) Biró Sándor (1949-) (molekuláris genetikus) Paholcsek Melinda (1984-) (molekuláris biológus, genetikus)
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2.

001-es BibID:BIBFORM072747
Első szerző:Morton, C. Oliver
Cím:Determining the analytical specificity of PCR-based assays for the diagnosis of IA : what is Aspergillus? / C. Oliver Morton, P. Lewis White, Rosemary A. Barnes, Lena Klingspor, Manuel Cuenca-Estrella, Katrien Lagrou, Stéphane Bretagne, Willem Melchers, Carlo Mengoli, Angela M. Caliendo, Massimo Cogliati, Yvette Debets-Ossenkopp, Rebecca Gorton, Ferry Hagen, Catriona Halliday, Petr Hamal, Kathleen Harvey-Wood, Katia Jaton, Gemma Johnson, Sarah Kidd, Martina Lengerova, Cornelia Lass-Florl, Chris Linton, Laurence Millon, C. Orla Morrissey, Melinda Paholcsek, Alida Fe Talento, Markus Ruhnke, Birgit Willinger, J. Peter Donnelly, Juergen Loeffler, EAPCRI
Dátum:2017
ISSN:1369-3786
Megjegyzések:A wide array of PCR tests has been developed to aid the diagnosis of invasive aspergillosis (IA), providing technical diversity but limiting standardisation and acceptance. Methodological recommendations for testing blood samples using PCR exist, based on achieving optimal assay sensitivity to help exclude IA. Conversely, when testing more invasive samples (BAL, biopsy, CSF) emphasis is placed on confirming disease, so analytical specificity is paramount. This multicenter study examined the analytical specificity of PCR methods for detecting IA by blind testing a panel of DNA extracted from a various fungal species to explore the range of Aspergillus species that could be detected, but also potential cross reactivity with other fungal species. Positivity rates were calculated and regression analysis was performed to determine any associations between technical specifications and performance. The accuracy of Aspergillus genus specific assays was 71.8%, significantly greater (P < .0001) than assays specific for individual Aspergillus species (47.2%). For genus specific assays the most often missed species were A. lentulus (25.0%), A. versicolor (24.1%), A. terreus (16.1%), A. flavus (15.2%), A. niger (13.4%), and A. fumigatus (6.2%). There was a significant positive association between accuracy and using an Aspergillus genus PCR assay targeting the rRNA genes (P = .0011). Conversely, there was a significant association between rRNA PCR targets and false positivity (P = .0032). To conclude current Aspergillus PCR assays are better suited for detecting A. fumigatus, with inferior detection of most other Aspergillus species. The use of an Aspergillus genus specific PCR assay targeting the rRNA genes is preferential.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Aspergillus PCR
analytical specificity
cross reactivity
detection range
Megjelenés:Medical Mycology 55 : 4 (2017), p. 402-413. -
További szerzők:White, P. Lewis Barnes, Rosemary A. Klingspor, Lena Cuenca-Estrella, Manuel Lagrou, Katrien Bretagne, Stéphane Melchers, Willem Mengoli, Carlo Caliendo, Angela M. Cogliati, Massimo Debets-Ossenkopp, Yvette Gorton, Rebecca Hagen, Ferry Halliday, Catriona Hamal, Petr Harvey-Wood, Kathleen Jaton, Katia Johnson, Gemma Kidd, Sarah Lengerova, Martina Lass-Florl, Cornelia Linton, Chris Millon, Laurence Morrissey, C. Orla Paholcsek Melinda (1984-) (molekuláris biológus, genetikus) Talento, Alida Fe Ruhnke, Markus Willinger, Birgit Donnelly, J. Peter Loeffler, Juergen EAPCRI
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DOI
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3.

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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DOI
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4.

001-es BibID:BIBFORM078810
035-os BibID:(WoS)000537424500018 (Scopus)85082779709
Első szerző:Nagy Fruzsina (molekuláris biológus)
Cím:Farnesol increases the activity of echinocandins against Candida auris biofilms / Fruzsina Nagy, Zoltán Tóth, Lajos Daróczi, Adrien Székely, Andrew M. Borman, László Majoros, Renátó Kovács
Dátum:2019
ISSN:1369-3786
Megjegyzések: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 ?M2%). This was confirmed by microscope images of combination-exposed biofilms. Our study showed the prominent effect of farnesol with echinocandins against C. auris biofilms.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Medical Mycology. - 58 : 3 (2019), p. 404-407. -
További szerzők:Tóth Zoltán (1990-) (molekuláris biológus) Daróczi Lajos (1965-) (fizikus) Székely Adrien 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
ÚNKP-18-3
egyéb
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5.

001-es BibID:BIBFORM075660
035-os BibID:(WoS)000482422300008 (Scopus)85072327125
Első szerző:Nagy Fruzsina (molekuláris biológus)
Cím:Fluconazole is not inferior than caspofungin, micafungin or amphotericin B in the presence of 50% human serum against Candida albicans and Candida parapsilosis biofilms / Fruzsina Nagy, Zoltán Tóth, Aliz Bozó, András Czeglédi, István Rebenku, László Majoros, Renátó Kovács
Dátum:2019
ISSN:1369-3786
Megjegyzések:Biofilm formation is a relevant risk factor for mortality in candidemia. Data about serum-based susceptibility testing against Candida biofilms are scant; therefore, the activity of fluconazole, amphotericin B, caspofungin and micafungin was determined against Candida albicans and C. parapsilosis biofilms with or without 50% human serum using XTT-based assays. Serum caused a remarkable adverse effect regarding biofilm structure for both species. Additionally, the ratio of nonviable cells increased for C. parapsilosis biofilms, as confirmed by fluorescent microscopy and flow cytometry. Despite impaired biofilm development, traditionally biofilm-active antifungals, surprisingly, showed decreased activity against C. albicans biofilms in serum at concentrations ranging from 0.5 to 1 mg/l and from 0.015 to 1 mg/l for amphotericin B and echinocandins, respectively (P < .01-.05). However, C. parapsilosis showed higher susceptibility to these antifungals due to reduced biofilm mass and the fungicidal effect of serum at concentrations ranging from 0.015 to 1 mg/l and from 0.015 to 512 mg/l for amphotericin B and echinocandins, respectively (P < .01-.05). Fluconazole exerted better antifungal activity in serum than traditionally biofilm-active antifungals against both examined biofilms. For fluconazole, significant differences were observed in susceptibility between serum-treated and serum-free biofilms at concentrations ranging from 0.015 to 8 mg/l and from 0.03 to 512 mg/l for C. albicans and C. parapsilosis isolates, respectively (P < .01-.05). The high antifungal activity of fluconazole in 50% serum both against C. albicans and C. parapsilosis biofilms supports the utility of fluconazole prophylaxis to reduce the risk of catheter-associated fungal infections.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Candida spp.
biofilm
serum
fluconazole
echinocandin
Megjelenés:Medical Mycology. - 57 : 5 (2019), p. 573-581. -
További szerzők:Tóth Zoltán (1990-) (molekuláris biológus) Bozó Aliz (1984-) (biológus) Czeglédi András Rebenku István Majoros László (1966-) (szakorvos, klinikai mikrobiológus) Kovács Renátó László (1987-) (molekuláris biológus)
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6.

001-es BibID:BIBFORM070392
035-os BibID:(WoS)000444345000013 (Scopus)85066434323
Első szerző:Nagy Fruzsina (molekuláris biológus)
Cím:In vitro antifungal susceptibility patterns of planktonic and sessile Candida kefyr clinical isolates / Nagy Fruzsina, Bozó Aliz, Tóth Zoltán, Daróczi Lajos, Majoros László, Kovács Renátó
Dátum:2018
ISSN:1369-3786
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Medical Mycology. - 56 : 4 (2018), p. 493-500. -
További szerzők:Bozó Aliz (1984-) (biológus) Tóth Zoltán (1990-) (molekuláris biológus) Daróczi Lajos (1965-) (fizikus) Majoros László (1966-) (szakorvos, klinikai mikrobiológus) Kovács Renátó László (1987-) (molekuláris biológus)
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