Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole against Vulvovaginal Candida spp.

Czechowicz, Paulina; Neubauer, Damian; Nowicka, J; Kamysz, Wojciech; Gościniak, Grażyna

doi:10.3390/pharmaceutics13101589

Cited by 10 publications

(21 citation statements)

References 68 publications

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“…In our previous work, we compared the antifungal activity of two pairs of cationic lipopeptides against Candida strains isolated from vulvovaginal candidiasis. These compounds effectively eradicated the mature structure of the biofilm [26]. In in vitro studies using polystyrene plates, we have demonstrated the advantage of the newly synthesized cyclic analogs C 16 -CKKKKC-NH 2 and C 16 -CKRKKC-NH 2 over their linear counterparts in the antimicrobial activity against Candida in planktonic and biofilm form [26].…”

Section: Introductionmentioning

confidence: 89%

“…These compounds effectively eradicated the mature structure of the biofilm [26]. In in vitro studies using polystyrene plates, we have demonstrated the advantage of the newly synthesized cyclic analogs C 16 -CKKKKC-NH 2 and C 16 -CKRKKC-NH 2 over their linear counterparts in the antimicrobial activity against Candida in planktonic and biofilm form [26]. At the same time, we have already proven that the use of combination therapy in the form of the simultaneous action of antifungal fluconazole that is conventionally used in VVC and the tested lipopeptides could be equally promising-this time indicating the advantage of the linear compounds C 16 -KKKK-NH 2 and C 16 -KRKK-NH 2 [26].…”

Section: Introductionmentioning

confidence: 99%

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Activity of Novel Ultrashort Cyclic Lipopeptides against Biofilm of Candida albicans Isolated from VVC in the Ex Vivo Animal Vaginal Model and BioFlux Biofilm Model—A Pilot Study

Czechowicz

Nowicka

Neubauer

et al. 2022

IJMS

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In recent years, clinicians and doctors have become increasingly interested in fungal infections, including those affecting the mucous membranes. Vulvovaginal candidiasis (VVC) is no exception. The etiology of this infection remains unexplained to this day, as well as the role and significance of asymptomatic vaginal Candida colonization. There are also indications that in the case of VVC, standard methods of determining drug susceptibility to antifungal drugs may not have a real impact on their clinical effectiveness—which would explain, among other things, treatment failures and relapse rates. The aim of the study was to verify the promising results obtained previously in vitro using standard methods, in a newly developed ex vivo model, using tissue fragments of the mouse vagina. The main goal of the study was to determine whether the selected ultrashort cyclic lipopeptides (USCLs) and their combinations with fluconazole at specific concentrations are equally effective against Candida forming a biofilm directly on the surface of the vaginal epithelium. In addition, the verification was also performed with the use of another model for the study of microorganisms (biofilms) in vitro—the BioFlux system, under microfluidic conditions. The obtained results indicate the ineffectiveness of the tested substances ex vivo at concentrations eradicating biofilm in vitro. Nevertheless, the relatively most favorable and promising results were still obtained in the case of combination therapy—a combination of low concentrations of lipopeptides (mainly linear analogs) with mycostatic fluconazole. Additionally, using BioFlux, it was not possible to confirm the previously obtained results. However, an inhibiting effect of the tested lipopeptides on the development of biofilm under microfluidic conditions was demonstrated. There is an incompatibility between the classic in vitro methods, the newer BioFlux method of biofilm testing, offering many advantages postulated elsewhere, and the ex vivo method. This incompatibility is another argument for the need, on the one hand, to intensify research on the pathomechanism of VVC, and, on the other hand, to verify and maybe modify the standard methods used in the determination of Candida susceptibility.

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Activity of Novel Ultrashort Cyclic Lipopeptides against Biofilm of Candida albicans Isolated from VVC in the Ex Vivo Animal Vaginal Model and BioFlux Biofilm Model—A Pilot Study

Czechowicz

Nowicka

Neubauer

et al. 2022

IJMS

Self Cite

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“…Other promising novel compounds like beta-glucan synthase inhibitor SCY-078, ion chelator DIBI, TOR inhibitor AZD8055, efflux modulators, and a group of novel antifungal chalcones have all proven highly synergistic against azole-resistant C. albicans, C. glabrata and other Candida species with reduced sensitivity to azoles [173,252,253,255,260]. A group of novel ultra-short cationic lipopeptides were not able to fully synergise with fluconazole, but did interact additively [259].…”

Section: Azole Synergy With Novel Compoundsmentioning

confidence: 99%

Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox

Kane

Carter

2022

Pharmaceuticals

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Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal arsenal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to resistance such as active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosages, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strategies.

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“…Other promising novel compounds like beta-glucan synthase inhibitor SCY-078, ion chelator DIBI, TOR inhibitor AZD8055, efflux modulators, and a group of novel antifungal chalcones have all proven highly synergistic against azole-resistant C. albicans, C. glabrata and other Candida species with reduced sensitivity to azoles [168,246,247,249,254]. A group of novel ultra-short cationic lipopeptides were not able to fully synergise with fluconazole, but did interact additively [253].…”

Section: Azole Synergy With Novel Compoundsmentioning

confidence: 99%

Augmenting Azoles with Drug Synergy to Expand The Antifungal Toolbox

Kane¹,

Carter²

2022

Preprint

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Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal ar-senal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to re-sistance like active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosag-es, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strate-gies.

show abstract

Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole against Vulvovaginal Candida spp.

Cited by 10 publications

References 68 publications

Activity of Novel Ultrashort Cyclic Lipopeptides against Biofilm of Candida albicans Isolated from VVC in the Ex Vivo Animal Vaginal Model and BioFlux Biofilm Model—A Pilot Study

Activity of Novel Ultrashort Cyclic Lipopeptides against Biofilm of Candida albicans Isolated from VVC in the Ex Vivo Animal Vaginal Model and BioFlux Biofilm Model—A Pilot Study

Augmenting Azoles with Drug Synergy to Expand the Antifungal Toolbox

Augmenting Azoles with Drug Synergy to Expand The Antifungal Toolbox

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