Synergistic activity of magnolol with azoles and its possible antifungal mechanism against<i>Candida albicans</i>

Sun, Libo; Liao, Kai; Liang, Shijing; Yu, Ping; Wang, D.-Y.

doi:10.1111/jam.12737

Cited by 61 publications

(40 citation statements)

References 40 publications

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“…C. elegans survival analysis was performed as previously described1329. C. albicans was seeded on plates containing brain heart infusion (BHI) and kanamycin (45 μg/mL).…”

Section: Methodsmentioning

confidence: 99%

microRNAs Involved in the Control of Innate Immunity in Candida Infected Caenorhabditis elegans

Sun

Zhi

Shakoor

et al. 2016

Sci Rep

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The role of microRNAs (miRNAs) in regulating innate immune response to Candida albicans infection in Caenorhabditis elegans is still largely unclear. Using small RNA SOLiD deep sequencing technique, we profiled the miRNAs that were dysregulated by C. albicans infection. We identified 16 miRNAs that were up-regulated and 4 miRNAs that were down-regulated in nematodes infected with C. albicans. Bioinformatics analysis implied that these dysregulated miRNAs may be involved in the control of many important biological processes. Using available mutants, we observed that mir-251 and mir-252 loss-of-function mutants were resistant to C. albicans infection, whereas mir-360 mutants were hypersensitive to C. albicans infection. The expression pattern of antimicrobial genes suggested that mir-251, mir-252, and mir-360 played crucial roles in regulating the innate immune response to C. albicans infection. Fungal burden might be closely associated with altered lifespan and innate immune response in mir-251, mir-252, and mir-360 mutants. Moreover, mir-251 and mir-252 might function downstream of p38 mitogen activated protein kinase (MAPK) or IGF-1/insulin-like pathway to regulate the innate immune response to C. albicans infection. Our results provide an important molecular basis for further elucidating how miRNA-mRNA networks may control the innate immune response to C. albicans infection.

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“…C. elegans survival analysis was performed as previously described1329. C. albicans was seeded on plates containing brain heart infusion (BHI) and kanamycin (45 μg/mL).…”

Section: Methodsmentioning

confidence: 99%

microRNAs Involved in the Control of Innate Immunity in Candida Infected Caenorhabditis elegans

Sun

Zhi

Shakoor

et al. 2016

Sci Rep

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“…Sulfa drugs exert potent synergistic activity with fluconazole (checkerboard assay). We assessed the activity of sulfa drugs in combination with fluconazole against azole-resistant Candida strains using the checkerboard assay (25)(26)(27)(28). As shown in Table 1, 15 sulfa drugs were found to exhibit synergistic relationships with fluconazole against 7 of the 10 Candida strains tested with fractional inhibitory concentration (⌺FIC) values ranging from Ͻ0.0312 to Ͻ0.25.…”

Section: Resultsmentioning

confidence: 99%

“…The activity of most azole resensitizing drugs has been attributed mainly to their ability to inhibit the overexpression of efflux pumps in Candida (35)(36)(37). Hence, we turned our attention to studying the effects of sulfa drugs on the efflux pump in Candida using a rhodamine 123 accumulation assay (27). The sulfa drugs did not affect the accumulation of rhodamine dye inside the Candida cells and therefore did not result in efflux pump inhibition (Fig.…”

Section: Figmentioning

confidence: 99%

Reversal of Azole Resistance in Candida albicans by Sulfa Antibacterial Drugs

Eldesouky

Mayhoub

Hazbun

et al. 2018

Antimicrob Agents Chemother

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Invasive candidiasis presents an emerging global public health challenge due to the emergence of resistance to the frontline treatment options, such as fluconazole. Hence, the identification of other compounds capable of pairing with fluconazole and averting azole resistance would potentially prolong the clinical utility of this important group. In an effort to repurpose drugs in the field of antifungal drug discovery, we explored sulfa antibacterial drugs for the purpose of reversing azole resistance in In this study, we assembled and investigated a library of 21 sulfa antibacterial drugs for their ability to restore fluconazole sensitivity in Surprisingly, the majority of assayed sulfa drugs (15 of 21) were found to exhibit synergistic relationships with fluconazole by checkerboard assay with fractional inhibitory concentration index (ΣFIC) values ranging from <0.0312 to 0.25. Remarkably, five sulfa drugs were able to reverse azole resistance in a clinically achievable range. The structure-activity relationships (SARs) of the amino benzene sulfonamide scaffold as antifungal agents were studied. We also identified the possible mechanism of the synergistic interaction of sulfa antibacterial drugs with azole antifungal drugs. Furthermore, the ability of sulfa antibacterial drugs to inhibit biofilm by 40% was confirmed. In addition, the effects of sulfa-fluconazole combinations on growth kinetics and efflux machinery were explored. Finally, using a infection model, we demonstrated that the sulfa-fluconazole combination does possess potent antifungal activity , reducing in infected worms by ∼50% compared to the control.

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“…investigated using standard broth microdilution checkerboard assays, following previously reported protocols [42][43][44] . The fractional inhibitory concentration index (ΣFICI) was used to assess the relationship between the combination of azole drugs with each stilbene derivative.…”

Section: Microdilution Checkerboard Assays the Interaction Between Smentioning

confidence: 99%

Ospemifene displays broad-spectrum synergistic interactions with itraconazole through potent interference with fungal efflux activities

Eldesouky

Salama

Hazbun

et al. 2020

Sci Rep

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Azole antifungals are vital therapeutic options for treating invasive mycotic infections. However, the emergence of azole-resistant isolates combined with limited therapeutic options presents a growing challenge in medical mycology. to address this issue, we utilized microdilution checkerboard assays to evaluate nine stilbene compounds for their ability to interact synergistically with azole drugs, particularly against azole-resistant fungal isolates. ospemifene displayed the most potent azole chemosensitizing activity, and its combination with itraconazole displayed broad-spectrum synergistic interactions against Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus (Σfici = 0.05-0.50). Additionally, in a Caenorhabditis elegans infection model, the ospemifene-itraconazole combination significantly reduced fungal CFU burdens in infected nematodes by ~75-96%. Nile Red efflux assays and RT-qPCR analysis suggest ospemifene interferes directly with fungal efflux systems, thus permitting entry of azole drugs into fungal cells. This study identifies ospemifene as a novel antifungal adjuvant that augments the antifungal activity of itraconazole against a broad range of fungal pathogens.

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Synergistic activity of magnolol with azoles and its possible antifungal mechanism againstCandida albicans

Abstract: Our results provide the first evidence that magnolol may function as a Cdr1p substrate and as an inhibitor of ergosterol biosynthesis. This function can thus be exploited in combination with azoles to reverse multidrug resistance of C. albicans strains.

Cited by 61 publications

References 40 publications

microRNAs Involved in the Control of Innate Immunity in Candida Infected Caenorhabditis elegans

microRNAs Involved in the Control of Innate Immunity in Candida Infected Caenorhabditis elegans

Reversal of Azole Resistance in Candida albicans by Sulfa Antibacterial Drugs

Ospemifene displays broad-spectrum synergistic interactions with itraconazole through potent interference with fungal efflux activities

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