Detection of inhibitors of Candida albicans Cdr transporters using a diS-C3(3) fluorescence

Szczepaniak, Joanna; Łukaszewicz, Marcin; Krasowska, Anna

doi:10.3389/fmicb.2015.00176

Cited by 24 publications

(25 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous investigations, we observed different influences on the Cdr1 transporter when combinations of FLC-beauvericin and diS-C3(3)-beauvericin were applied in which beauvericin was an inhibitor of the ABC transporters and diS-C3(3) was the substrate for these pumps [44]. Similar differences in inhibitory activity were observed for curcumin [45], the modulatory effect of which was restricted to R6G or miconazole, while it had no effect on the efflux of FLC.…”

Section: Discussionsupporting

confidence: 56%

Antifungal Styryloquinolines as Candida albicans Efflux Pump Inhibitors: Styryloquinolines are ABC Transporter Inhibitors

et al. 2020

Self Cite

View full text Add to dashboard Cite

Styrylquinolines are heterocyclic compounds that are known for their antifungal and antimicrobial activity. Metal complexation through hydroxyl groups has been claimed to be a plausible mechanism of action for these types of compounds. A series of novel structures with protected hydroxyl groups have been designed and synthesized to verify the literature data. Their antifungal activity against wild-type Candida albicans strain and mutants with silenced efflux pumps activity has been determined. Combinations with fluconazole revealed synergistic interactions that were dependent on the substitution pattern. These results open a new route for designing active antifungal agents on a styrylquinoline scaffold.

show abstract

Section: Discussionsupporting

confidence: 56%

Antifungal Styryloquinolines as Candida albicans Efflux Pump Inhibitors: Styryloquinolines are ABC Transporter Inhibitors

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…We previously demonstrated that beauvericin inhibits multidrug efflux in S. cerevisiae, and a recent study suggests that beauvericin inhibits the C. albicans ABC transporters Cdr1 and Cdr2 (22,29). To determine whether beauvericin potentiates azole activity via inhibition of multidrug efflux in C. albicans, we assessed the drug synergy against strains lacking the ABC transporter genes CDR1 and CDR2 both individually and in combination.…”

Section: Resultsmentioning

confidence: 99%

Beauvericin Potentiates Azole Activity via Inhibition of Multidrug Efflux, Blocks Candida albicans Morphogenesis, and Is Effluxed via Yor1 and Circuitry Controlled by Zcf29

Shekhar-Guturja

Tebung

Mount

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Invasive fungal infections are a leading cause of human mortality. Effective treatment is hindered by the rapid emergence of resistance to the limited number of antifungal drugs, demanding new strategies to treat life-threatening fungal infections. Here, we explore a powerful strategy to enhance antifungal efficacy against leading human fungal pathogens by using the natural product beauvericin. We found that beauvericin potentiates the activity of azole antifungals against azole-resistant Candida isolates via inhibition of multidrug efflux and that beauvericin itself is effluxed via Yor1. As observed in Saccharomyces cerevisiae, we determined that beauvericin inhibits TOR signaling in Candida albicans. To further characterize beauvericin activity in C. albicans, we leveraged genome sequencing of beauvericin-resistant mutants. Resistance was conferred by mutations in transcription factor genes TAC1, a key regulator of multidrug efflux, and ZCF29, which was uncharacterized. Transcriptional profiling and chromatin immunoprecipitation coupled to microarray analyses revealed that Zcf29 binds to and regulates the expression of multidrug transporter genes. Beyond drug resistance, we also discovered that beauvericin blocks the C. albicans morphogenetic transition from yeast to filamentous growth in response to diverse cues. We found that beauvericin represses the expression of many filament-specific genes, including the transcription factor BRG1. Thus, we illuminate novel circuitry regulating multidrug efflux and establish that simultaneously targeting drug resistance and morphogenesis provides a promising strategy to combat life-threatening fungal infections.

show abstract

“…Screens for inhibitors can be based on yeast growth measurements that demonstrate the reversal of fungal resistance to a pump substrate such as the azoles (chemosensitization) or can utilize the fluorescent properties of certain pump substrates such as rhodamine 6G (R6G) [54,74,75], Nile Red [76] or diS-C3 [77]. However, as noted above, growth chemosensitization assays, unless targeted to counter efflux-mediated resistance, may identify interference with one or more different aspects of resistance, not necessarily involving efflux.…”

Section: Screening Methods To Identify Inhibitors Of Fungal Efflux Pumpsmentioning

confidence: 99%

Targeting Efflux Pumps to Overcome Antifungal Drug Resistance

et al. 2016

View full text Add to dashboard Cite

Resistance to antifungal drugs is an increasingly significant clinical problem. The most common antifungal resistance encountered is efflux pump-mediated resistance of Candida species to azole drugs. One approach to overcome this resistance is to inhibit the pumps and chemosensitize resistant strains to azole drugs. Drug discovery targeting fungal efflux pumps could thus result in the development of azole-enhancing combination therapy. Heterologous expression of fungal efflux pumps in Saccharomyces cerevisiae provides a versatile system for screening for pump inhibitors. Fungal efflux pumps transport a range of xenobiotics including fluorescent compounds. This enables the use of fluorescence-based detection, as well as growth inhibition assays, in screens to discover compounds targeting efflux-mediated antifungal drug resistance. A variety of medium- and high-throughput screens have been used to identify a number of chemical entities that inhibit fungal efflux pumps.

show abstract

Detection of inhibitors of Candida albicans Cdr transporters using a diS-C3(3) fluorescence

Cited by 24 publications

References 33 publications

Antifungal Styryloquinolines as Candida albicans Efflux Pump Inhibitors: Styryloquinolines are ABC Transporter Inhibitors

Antifungal Styryloquinolines as Candida albicans Efflux Pump Inhibitors: Styryloquinolines are ABC Transporter Inhibitors

Beauvericin Potentiates Azole Activity via Inhibition of Multidrug Efflux, Blocks Candida albicans Morphogenesis, and Is Effluxed via Yor1 and Circuitry Controlled by Zcf29

Targeting Efflux Pumps to Overcome Antifungal Drug Resistance

Contact Info

Product

Resources

About