Abrogation of efflux pump activity, biofilm formation, and immune escape by candidacidal geraniol in emerging superbug, Candida auris

Fatima, Tazeen; Fatima, Zeeshan; Hameed, Saif

doi:10.1007/s10123-023-00343-3

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…The synergistic effect for AmB and echinocandins observed in vitro was further assessed in vivo , using the C. elegans host model, to establish a possible correlation. The nematode C. elegans has been shown to be useful as host model of Candida infection to increase knowledge of the virulence and the efficacy of treatments for candidiasis caused by different Candida species ( 25 , 57 ), including C. auris ( 8 , 26 – 31 ). Concretely, combination therapy studies of C. elegans infected with C. auris have been conducted to evaluate the combination of azoles with other drugs, such as sulfamethoxazole ( 26 ), the HIV protease inhibitor lopinavir ( 27 ), the antiemetic agent aprepitant ( 28 ), and the stilbene compound ospemifene ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

“…The nematode Caenorhabditis elegans is a widely used alternative host model of candidiasis because of its simplicity, the possibility of using a very large number of individuals in each assay, and the rapid achievement of results. As such, it is a suitable non-mammalian host model for studying the virulence of Candida spp., including C. auris ( 8 , 26 – 31 ), as well as the efficacy of antifungal drugs and new antifungal compounds as treatments for candidiasis ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model

Hernando-Ortiz,

Eraso,

Jauregizar

et al. 2024

Microbiol Spectr

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The multidrug-resistant Candida auris is a global health emergency, being responsible for outbreaks of invasive candidiasis worldwide. Limited effective therapeutic options make it difficult to treat this emerging pathogen. In this context, combinations of different antifungal drugs are considered a promising therapeutic alternative. The aim of this work was to analyze the antifungal activity of combinations of amphotericin B and echinocandins against five clinical blood isolates of C. auris . One of these isolates showed an aggregative phenotype already described in C. auris species, forming large aggregates of cells that are very difficult to disintegrate. First, the in vitro activity of these drugs was evaluated both in monotherapy and in combination, and results showed synergistic interactions between amphotericin B and echinocandins in most cases, although higher minimum inhibitory concentration (MIC) values were observed against the aggregative isolate compared to non-aggregative counterparts. The most promising drug combinations were then selected for in vivo activity evaluation using a Caenorhabditis elegans model of candidiasis and by determination of survival rates. The combination of amphotericin B and caspofungin showed the strongest protective effect during C. elegans infection with C. auris blood isolates, achieving up to 99% C . elegans survival. Although the MIC values for micafungin were low in vitro , these drug concentrations had no effect in vivo , and the combination of amphotericin B and micafungin was the least effective. The results of this study showed that the combination amphotericin B and echinocandins might be a promising therapeutic approach for the treatment of invasive candidiasis caused by C. auris . Moreover, the nematode C. elegans is a suitable alternative model for screening of new therapeutic agents capable of overcoming multidrug-resistant C. auris infections. IMPORTANCE Multidrug resistance is a rising problem among non- Candida albicans species, such as Candida auris . This therapeutic problem has been very important during the COVID-19 pandemic. The World Health Organization has included C. auris in its global priority list of health-threatening fungi, to study this emerging multidrug-resistant species and to develop effective alternative therapies. In the present study, the synergistic effect of the combination of amphotericin B and echinocandins has been demonstrated against blood isolates of C. auris . Different susceptibility responses were also observed between aggregative and non-aggregative phenotypes. The antifungal activity of these drug combinations against C. auris was also demonstrated in the Caenorhabditis elegans host model of candidiasis, confirming the suitability and usefulness of this model in the search for solutions to antimicrobial resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model

Hernando-Ortiz,

Eraso,

Jauregizar

et al. 2024

Microbiol Spectr

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“…Geraniol displayed fungicidal activity and inhibition effect on metabolically active biofilm of C. auris. Subsequently, geraniol improved the survival rate of C. elegans infected by C. auris [58].…”

Section: Natural Products Against Candida Aurismentioning

confidence: 99%

Current Perspectives of Antifungal Therapy: A Special Focus on <em>Candida auris</em>

Arumugam,

Muthuselvam,

Lima

et al. 2024

Preprint

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Candida auris is considered an emerging Candida species that has rapidly spread all over the world. The evidence of its origin and emerging resistance is still unclear. The severe infection by this species causes significant mortality and morbidity among the elderly and immune compressed individuals. Development of drug resistance is the major factor associated with therapeutic failure of existing antifungal agents. Previous studies addressed the antifungal resistance profile and drug discovery for C. auris. However, comprehensive coverage of these information in a single investigation yet to be available. In this review, we have mainly focused on recent development in therapeutic strategy against C. auris. Based on the available information, several differential approaches were discussed, including existing antifungal drugs, chemical compounds, essential oils, natural products, antifungal peptides, immunotherapy, antimicrobial photodynamic therapy, drug repurposing, and drug delivery systems. Among them, chemical medications, natural products, and antifungal peptides are the prime contributors. However, a limited number of resources are available to prove the efficiency of these potential therapies in clinical usage. Hence, we hope that the data gathered in this review can encourage in vivo studies and clinical trials.

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“…Geraniol displayed fungicidal activity and an inhibition effect on the metabolically active biofilm of C. auris . Subsequently, geraniol improved the survival rate of C. elegans infected by C. auris [ 70 ].…”

Section: Therapeutic Optionsmentioning

confidence: 99%

Current Perspectives of Antifungal Therapy: A Special Focus on Candida auris

Ganeshkumar,

Muthuselvam,

Lima

et al. 2024

JoF

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Candida auris is an emerging Candida sp. that has rapidly spread all over the world. The evidence regarding its origin and emerging resistance is still unclear. The severe infection caused by this species results in significant mortality and morbidity among the elderly and immunocompromised individuals. The development of drug resistance is the major factor associated with the therapeutic failure of existing antifungal agents. Previous studies have addressed the antifungal resistance profile and drug discovery for C. auris. However, complete coverage of this information in a single investigation is not yet available. In this review, we have mainly focused on recent developments in therapeutic strategies against C. auris. Based on the available information, several different approaches were discussed, including existing antifungal drugs, chemical compounds, essential oils, natural products, antifungal peptides, immunotherapy, antimicrobial photodynamic therapy, drug repurposing, and drug delivery systems. Among them, synthetic chemicals, natural products, and antifungal peptides are the prime contributors. However, a limited number of resources are available to prove the efficiency of these potential therapies in clinical usage. Therefore, we anticipate that the findings gathered in this review will encourage further in vivo studies and clinical trials.

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Abrogation of efflux pump activity, biofilm formation, and immune escape by candidacidal geraniol in emerging superbug, Candida auris

Cited by 5 publications

References 39 publications

Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model

Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model

Current Perspectives of Antifungal Therapy: A Special Focus on <em>Candida auris</em>

Current Perspectives of Antifungal Therapy: A Special Focus on Candida auris

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