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  • 1
    Online Resource
    Online Resource
    Fluconazole and Lipopeptide Surfactin Interplay During Candida albicans Plasma Membrane and Cell Wall Remodeling Increases Fungal Immune System Exposure
    MDPI AG ; 2020
    In:  Pharmaceutics Vol. 12, No. 4 ( 2020-04-01), p. 314-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 12, No. 4 ( 2020-04-01), p. 314-
    Abstract: Recognizing the β-glucan component of the Candida albicans cell wall is a necessary step involved in host immune system recognition. Compounds that result in exposed β-glucan recognizable to the immune system could be valuable antifungal drugs. Antifungal development is especially important because fungi are becoming increasingly drug resistant. This study demonstrates that lipopeptide, surfactin, unmasks β-glucan when the C. albicans cells lack ergosterol. This observation also holds when ergosterol is depleted by fluconazole. Surfactin does not enhance the effects of local chitin accumulation in the presence of fluconazole. Expression of the CHS3 gene, encoding a gene product resulting in 80% of cellular chitin, is downregulated. C. albicans exposure to fluconazole changes the composition and structure of the fungal plasma membrane. At the same time, the fungal cell wall is altered and remodeled in a way that makes the fungi susceptible to surfactin. In silico studies show that surfactin can form a complex with β-glucan. Surfactin forms a less stable complex with chitin, which in combination with lowering chitin synthesis, could be a second anti-fungal mechanism of action of this lipopeptide.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics12040314
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 2
    Online Resource
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    Lipid composition and cell surface hydrophobicity of Candida albicans influence the efficacy of fluconazole–gentamicin treatment
    Wiley ; 2020
    In:  Yeast Vol. 37, No. 1 ( 2020-01), p. 117-129
    Details
    In: Yeast, Wiley, Vol. 37, No. 1 ( 2020-01), p. 117-129
    Abstract: Adherence of the fungus, Candida albicans , to biotic (e.g. human tissues) and abiotic (e.g. catheters) surfaces can lead to emergence of opportunistic infections in humans. The process of adhesion and further biofilm development depends, in part, on cell surface hydrophobicity (CSH). In this study, we compared the resistance of C. albicans strains with different CSH to the most commonly prescribed antifungal drug, fluconazole, and the newly described synergistic combination, fluconazole and gentamicin. The hydrophobic strain was more resistant to fluconazole due to, among others, overexpression of the ERG11 gene encoding the fluconazole target protein (CYP51A1, Erg11p), which leads to overproduction of ergosterol in this strain. Additionally, the hydrophobic strain displayed high efflux activity of the multidrug resistance Cdr1 pump due to high expression of the CDR1 gene. On the other hand, the hydrophobic C. albicans strain was more susceptible to fluconazole–gentamicin combination because of its different effect on lipid content in the two strains. The combination resulted in ergosterol depletion with subsequent Cdr1p mislocalization and loss of activity in the hydrophobic strain. We propose that C. albicans strains with different CSH may possess altered lipid metabolism and consequently may differ in their response to treatment.
    Type of Medium: Online Resource
    ISSN: 0749-503X , 1097-0061
    URL: Issue
    URL: Article
    DOI: 10.1002/yea.v37.1
    DOI: 10.1002/yea.3455
    RVK:
    WA 15000
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 1479172-9
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    The influence of N and S poles of static magnetic field (SMF) on Candida albicans hyphal formation and antifungal activity of amphotericin B
    Springer Science and Business Media LLC ; 2019
    In:  Folia Microbiologica Vol. 64, No. 6 ( 2019-11), p. 727-734
    Details
    In: Folia Microbiologica, Springer Science and Business Media LLC, Vol. 64, No. 6 ( 2019-11), p. 727-734
    Type of Medium: Online Resource
    ISSN: 0015-5632 , 1874-9356
    URL: Article
    DOI: 10.1007/s12223-019-00686-3
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2209844-6
    SSG: 12
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  • 4
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    Lactate Like Fluconazole Reduces Ergosterol Content in the Plasma Membrane and Synergistically Kills Candida albicans
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 10 ( 2021-05-14), p. 5219-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 10 ( 2021-05-14), p. 5219-
    Abstract: Candida albicans is an opportunistic pathogen that induces vulvovaginal candidiasis (VVC), among other diseases. In the vaginal environment, the source of carbon for C. albicans can be either lactic acid or its dissociated form, lactate. It has been shown that lactate, similar to the popular antifungal drug fluconazole (FLC), reduces the expression of the ERG11 gene and hence the amount of ergosterol in the plasma membrane. The Cdr1 transporter that effluxes xenobiotics from C. albicans cells, including FLC, is delocalized from the plasma membrane to a vacuole under the influence of lactate. Despite the overexpression of the CDR1 gene and the increased activity of Cdr1p, C. albicans is fourfold more sensitive to FLC in the presence of lactate than when glucose is the source of carbon. We propose synergistic effects of lactate and FLC in that they block Cdr1 activity by delocalization due to changes in the ergosterol content of the plasma membrane.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22105219
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 5
    Online Resource
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    A Crucial Role for Ergosterol in Plasma Membrane Composition, Localisation, and Activity of Cdr1p and H+-ATPase in Candida albicans
    MDPI AG ; 2019
    In:  Microorganisms Vol. 7, No. 10 ( 2019-09-22), p. 378-
    Details
    In: Microorganisms, MDPI AG, Vol. 7, No. 10 ( 2019-09-22), p. 378-
    Abstract: Candida albicans is an opportunistic fungal pathogen of humans. Treatment of C. albicans infections relies on azoles, which target the lanosterol 14α-demethylase (Erg11p) encoded by the ERG11 gene. Our results show that targeted gene disruption of ERG11 can result in resistance to ergosterol-dependent drugs (azoles and amphotericin B), auxotrophy and aerobically viable erg11Δ/Δ cells. Abnormal sterol deposition and lack of ergosterol in the erg11Δ/Δ strain leads to reduced plasma membrane (PM) fluidity, as well as dysfunction of the vacuolar and mitochondrial membranes, resulting respectively in defects in vacuole fusion and a reduced intracellular ATP level. The altered PM structure of the erg11Δ/Δ strain contributes to delocalisation of H+-ATPase and the Cdr1 efflux pump from the PM to vacuoles and, resulting in a decrease in PM potential (Δψ) and increased sensitivity to ergosterol-independent xenobiotics. This new insight into intracellular processes under Erg11p inhibition may lead to a better understanding of the indirect effects of azoles on C. albicans cells and the development of new treatment strategies for resistant infections.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms7100378
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2720891-6
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  • 6
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    Online Resource
    S. pombe DNA translocases Rrp1 and Rrp2 have distinct roles at centromeres and telomeres that ensure genome stability
    The Company of Biologists ; 2020
    In:  Journal of Cell Science
    Details
    In: Journal of Cell Science, The Company of Biologists
    Abstract: The regulation of telomere and centromere structure and function is essential for maintaining genome integrity. Schizosaccharomyces pombe Rrp1 and Rrp2 are orthologues of Saccharomyces cerevisiae Uls1, a SWI2/SNF2 DNA translocase and SUMO-Targeted Ubiquitin Ligase. Here we show that Rrp1 or Rrp2 overproduction leads to chromosome instability and growth defects, a reduction of global histone levels and mislocalisation of centromere-specific histone Cnp1. These phenotypes depend on putative DNA translocase activities of Rrp1 and Rrp2, suggesting that Rrp1 and Rrp2 may be involved in modulating nucleosome dynamics. Furthermore, we confirm that Rrp2, but not Rrp1, acts at telomeres, reflecting a previously described interaction between Rrp2 and Top2. In conclusion, we identify roles for Rrp1 and Rrp2 in maintaining centromere function by modulating histone dynamics, contributing to the preservation of genome stability during vegetative cell growth.
    Type of Medium: Online Resource
    ISSN: 1477-9137 , 0021-9533
    URL: Article
    DOI: 10.1242/jcs.230193
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2020
    detail.hit.zdb_id: 219171-4
    detail.hit.zdb_id: 1483099-1
    SSG: 12
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  • 7
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    The Role of Ergosterol and Sphingolipids in the Localization and Activity of Candida albicans’ Multidrug Transporter Cdr1p and Plasma Membrane ATPase Pma1p
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 17 ( 2022-09-01), p. 9975-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 17 ( 2022-09-01), p. 9975-
    Abstract: Opportunistic pathogen Candida albicans causes systemic infections named candidiasis. Due to the increasing number of multi-drug resistant clinical isolates of Candida sp., currently employed antifungals (e.g., azoles) are insufficient for combating fungal infection. One of the resistance mechanisms toward azoles is increased expression of plasma membrane (PM) transporters (e.g., Cdr1p), and such an effect was observed in C. albicans clinical isolates. At the same time, it has been proven that a decrease in PMs sphingolipids (SLs) content correlates with altered sensitivity to azoles and diminished Cdr1p levels. This indicates an important role for SL in maintaining the properties of PM and gaining resistance to antifungal agents. Here, we prove using a novel spot variation fluorescence correlation spectroscopy (svFCS) technique that CaCdr1p localizes in detergent resistant microdomains (DRMs). Immunoblot analysis confirmed the localization of CaCdr1p in DRMs fraction in both the C. albicans WT and erg11Δ/Δ strains after 14 and 24 h of culture. We also show that the C. albicanserg11Δ/Δ strain is more sensitive to the inhibitor of SLs synthesis; aureobasidin A (AbA). AbA treatment leads to a diminished amount of SLs in C. albicans WT and erg11Δ/Δ PM, while, for C. albicanserg11Δ/Δ, the general levels of mannose-inositol-P-ceramide and inositol-P-ceramide are significantly lower than for the C. albicans WT strain. Simultaneously, the level of ergosterol in the C. albicans WT strain after adding of AbA remains unchanged, compared to the control conditions. Analysis of PM permeabilization revealed that treatment with AbA correlates with the disruption of PM integrity in C. albicanserg11Δ/Δ but not in the C. albicans WT strain. Additionally, in the C. albicans WT strain, we observed lower activity of H+-ATPase, correlated with the delocalization of both CaCdr1p and CaPma1p.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23179975
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 8
    Online Resource
    Online Resource
    Rrp1 translocase and ubiquitin ligase activities restrict the genome destabilising effects of Rad51 in fission yeast
    Oxford University Press (OUP) ; 2021
    In:  Nucleic Acids Research Vol. 49, No. 12 ( 2021-07-09), p. 6832-6848
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 49, No. 12 ( 2021-07-09), p. 6832-6848
    Abstract: Rad51 is the key protein in homologous recombination that plays important roles during DNA replication and repair. Auxiliary factors regulate Rad51 activity to facilitate productive recombination, and prevent inappropriate, untimely or excessive events, which could lead to genome instability. Previous genetic analyses identified a function for Rrp1 (a member of the Rad5/16-like group of SWI2/SNF2 translocases) in modulating Rad51 function, shared with the Rad51 mediator Swi5-Sfr1 and the Srs2 anti-recombinase. Here, we show that Rrp1 overproduction alleviates the toxicity associated with excessive Rad51 levels in a manner dependent on Rrp1 ATPase domain. Purified Rrp1 binds to DNA and has a DNA-dependent ATPase activity. Importantly, Rrp1 directly interacts with Rad51 and removes it from double-stranded DNA, confirming that Rrp1 is a translocase capable of modulating Rad51 function. Rrp1 affects Rad51 binding at centromeres. Additionally, we demonstrate in vivo and in vitro that Rrp1 possesses E3 ubiquitin ligase activity with Rad51 as a substrate, suggesting that Rrp1 regulates Rad51 in a multi-tiered fashion.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkab511
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    The alternating 50 Hz magnetic field depending on the hydrophobicity of the strain affects the viability, filamentation and sensitivity to drugs of Candida albicans
    Public Library of Science (PLoS) ; 2023
    In:  PLOS ONE Vol. 18, No. 10 ( 2023-10-5), p. e0291438-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 10 ( 2023-10-5), p. e0291438-
    Abstract: In recent decades, Candida albicans have been the main etiological agent of life-threatening invasive infections, characterized by various mechanisms of resistance to commonly used antifungals. One of the strategies to fight Candida infections may be the use of an electromagnetic field. In this study, we examined the influence of the alternating magnetic field of 50 Hz on the cells of C . albicans . We checked the impact of the alternating magnetic field of 50 Hz on the viability, filamentation and sensitivity to fluconazole and amphotericin B of two, differing in hydrophobicity, strains of C . albicans , CAF2-1 and CAF 4–2. Our results indicate that using the alternating magnetic field of 50 Hz reduces the growth of C . albicans . Interestingly, it presents a stronger effect on the hydrophobic strain CAF4-2 than on the hydrophilic CAF2-1. The applied electromagnetic field also affects the permeabilization of the cell membrane. However, it does not inhibit the transformation from yeast to hyphal forms. AMF is more effective in combination with fluconazole rather than amphotericin B. Our findings confirm the hypothesis that the application of the alternating magnetic field of 50 Hz in antifungal therapy may arise as a new option to support the treatment of Candida infections.
    Type of Medium: Online Resource
    ISSN: 1932-6203
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1371/journal.pone.0291438
    DOI: 10.1371/journal.pone.0291438.g001
    DOI: 10.1371/journal.pone.0291438.g002
    DOI: 10.1371/journal.pone.0291438.g003
    DOI: 10.1371/journal.pone.0291438.g004
    DOI: 10.1371/journal.pone.0291438.t001
    DOI: 10.1371/journal.pone.0291438.t002
    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2023
    detail.hit.zdb_id: 2267670-3
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  • 10
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    ROZPOWSZECHNIANIE REZULTATÓW PROJEKTÓW REALIZOWANYCH W RAMACH PROGRAMU UNII EUROPEJSKIEJ „HORYZONT 2020”
    Index Copernicus ; 2018
    In:  PRZEGLĄD POLICYJNY Vol. 3, No. 131 ( 2018-9-11), p. 31-40
    Details
    In: PRZEGLĄD POLICYJNY, Index Copernicus, Vol. 3, No. 131 ( 2018-9-11), p. 31-40
    Abstract: Rozpowszechnianie wyników projektów realizowanych w ramach grantów z funduszy unijnych, takich jak program „Horyzont 2020”, jest obowiązkiem wynikającym z umowy grantowej zawieranej pomiędzy koordynatorem reprezentującym dane konsorcjum projektowe, a Komisją Europejską (pozostali partnerzy konsorcjum przystępują do umowy grantowej poprzez podpisanie „formularzy przystąpienia”, które stanowią integralną część umowy). Wyniki projektów finansowanych poprzez inicjatywy i programy unijne muszą być rozpowszechniane, tak aby doświadczenia i wiedza zdobyte przez jeden zespół mogły służyć ogółowi środowiska naukowego i społeczeństwu. Co więcej, doświadczenia wyniesione z danego projektu powinny wpływać na kształtowanie ram przyszłych programów i projektów badawczych poprzez komunikowanie decydentom potrzeb świata nauki i przemysłu. W związku z powyższym, stworzenie przemyślanej i odpowiadającej charakterystyce danego projektu strategii i planu rozpowszechniania rezultatów ma kluczowe znaczenie dla uzyskania maksymalnego oddziaływania projektu na środowisko (naukowe i gospodarcze). W artykule wskazano dobre praktyki tworzenia strategii i planu rozpowszechniania rezultatów projektów. Autorzy artykułu omawiają dokumenty, które określają zasady wynikające z obowiązku rozpowszechniania wyników projektów przez członków konsorcjów, tj. umowa grantowa, umowa konsorcjum czy przewodnik dla wnioskodawców. Celem artykułu jest przybliżenie czytelnikom założeń wspomnianych dokumentów w odniesieniu do rozpowszechniania wyników projektów z uwagi na ważkość tego aspektu podczas realizacji projektów, gdyż recenzenci wniosków projektów oraz sama Komisja Europejska przykładają dużą wagę do promowania i rozpropagowywania projektów i wyników osiągniętych w ramach prac naukowo-badawczych.
    Type of Medium: Online Resource
    ISSN: 0867-5708
    URL: Journal
    URL: Article
    DOI: 10.5604/08675708
    DOI: 10.5604/01.3001.0013.6663
    Language: Polish
    Publisher: Index Copernicus
    Publication Date: 2018
    detail.hit.zdb_id: 3160131-5
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