Fluconazole Assists Berberine To Kill Fluconazole-Resistant Candida albicans

Li, Dedong; Xu, Yi; Zhang, Dazhi; Quan, Hua; Mylonakis, Eleftherios; Hu, Dandan; Li, Ming-Bang; Zhao, Lijie; Zhu, Liang-hua; Wang, Yan; Jiang, Yuanying

doi:10.1128/aac.00499-13

Cited by 71 publications

(62 citation statements)

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“…A recent study has demonstrated that berebrine can assist fluconazole to kill fluconazole-resistant C. albicans (32). The present results further indicate the possible sensitization of various pathogenic fungi to other standard drugs by berberine and berberrubine, with the purpose of obtaining an increment in the antifungal potency.…”

Section: Determination Of Mic Mfc and Sensitization Assaysupporting

confidence: 50%

Sensitization of Candida albicans to terbinafine by berberine and berberrubine

et al. 2016

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Abstract. Candida albicans (C. albicans) is an opportunistic fungal pathogen, particularly observed in immunocompromised patients. C. albicans accounts for 50-70% of cases of invasive candidiasis in the majority of clinical settings. Terbinafine, an allylamine antifungal drug, has been used to treat fungal infections previously. It has fungistatic activity against C. albicans. Traditional Chinese medicines can be used as complementary medicines to conventional drugs to treat a variety of ailments and diseases. Berberine is a quaternary alkaloid isolated from the traditional Chinese herb, Coptidis Rhizoma, while berberrubine is isolated from the medicinal plant Berberis vulgaris, but is also readily derived from berberine by pyrolysis. The present study demonstrates the possible complementary use of berberine and berberrubine with terbinafine against C. albicans. The experimental findings assume that the potential application of these alkaloids together with reduced dosage of the standard drug would enhance the resulting antifungal potency.

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Section: Determination Of Mic Mfc and Sensitization Assaysupporting

confidence: 50%

Sensitization of Candida albicans to terbinafine by berberine and berberrubine

et al. 2016

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“…Collectively, based on the present results, it may be speculated that IMP had synergistic effects with BEB via increasing the accumulation of BEB in the intracellular space of P. aeruginosa cells. However, whether the ingressive BEB finally caused cell cycle arrest and DNA damage similar to its effects in Candida albicans still requires to be elucidated (13).…”

Section: Discussionmentioning

confidence: 99%

“…Due to this IMP resistance in P. aeruginosa novel antibacterial agents are urgently required. Berberine (BEB), a natural isoquinoline alkaloid, is prevalent in numerous medicinal plants and has been demonstrated to have antibacterial and antifungal activities alone or in combination with other drugs (9)(10)(11)(12)(13). In a previous study, BEB was reported to be a potential inhibitor of MexXY-mediated resistance in P. aeruginosa (14).…”

Section: Introductionmentioning

confidence: 99%

Berberine inhibits the MexXY‑OprM efflux pump to reverse imipenem resistance in a clinical carbapenem‑resistant Pseudomonas aeruginosa isolate in a planktonic state

Fen

Wang

2017

Exp Ther Med

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Abstract. Pseudomonas (P.) aeruginosa is an ubiquitous and metabolically versatile opportunistic pathogen and may cause various life-threatening diseases. Due to increasing emergence of resistance to carbapenems, novel drugs with improved antibacterial activities compared with those of traditional antibiotics are required. In the present study, berberine (BEB), a natural isoquinoline alkaloid, was used in combination with imipenem (IMP), a commonly-used carbapenem, to investigate their antibacterial activities against a clinical P. aeruginosa isolate PA012 and the potential mechanism. Screening revealed that the minimum inhibitory concentrations (MICs) of BEB and IMP were 512 and 256 µg/ml, respectively. The combination of BEB (1/4 MIC) and IMP (1/8 MIC) exhibited a synergistic effect with a fractional inhibitory concentration index of 0.375. The synergism of BEB and IMP was also demonstrated in a time-kill test and by scanning electron microscopic observation. Treatment with BEB at ¼ MIC in combination with IMP at 1/16, 1/8, 1/4 and ½ MIC revealed a concentration-dependent promoting effect of IMP on the intracellular accumulation of BEB and inhibition of bacterial adhesion. Further analysis of gene expression revealed that BEB (1/4 MIC) combined with IMP (1/8 MIC) decreased MexZ, MexX, MexY and outer membrane protein (Opr)M by 38, 35, 46 and 49% in PA012. In conclusion, these results suggested that IMP had synergistic effects with BEB against the clinical isolate PA012 via inhibition of the MexXY-OprM efflux pump.

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“…FCZ is undergoing clinical testing and has been shown to have minimal toxicity (3,34). Many strains of C. albicans are resistant to FCZ therapy, while FCZ can be cytotoxic at high concentrations (15,35).…”

Section: Discussionmentioning

confidence: 99%

“…This yeast normally lives on the skin and mucous membranes without causing infection. However, overgrowth of these microbes can cause superficial mycoses, invasive mucosal infections, and disseminated systemic disease, particularly in AIDS patients, transplant recipients, and other immunocompromised people (2,3). It is well documented that the emergence of drug-resistant C. albicans is increasing at an alarming pace (4)(5)(6).…”

mentioning

confidence: 99%

Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing

Singh

Upreti

Singh

et al. 2015

Antimicrob Agents Chemother

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dQuorum sensing (QS) regulates group behaviors of Candida albicans such as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced by C. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment of C. albicans infections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnea longissima), can be implemented as a sensitizing agent for FCZresistant C. albicans NBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons-biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZmediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy of C. albicans infections. Candidiasis is a prevalent fungal infection caused by species of the yeast genus Candida. There are more than Candida 20 species, the most common of which is Candida albicans. Candidiasis is the fourth most common cause of health care-associated bloodstream infections in India and the United States (1). This yeast normally lives on the skin and mucous membranes without causing infection. However, overgrowth of these microbes can cause superficial mycoses, invasive mucosal infections, and disseminated systemic disease, particularly in AIDS patients, transplant recipients, and other immunocompromised people (2, 3). It is well documented that the emergence of drug-resistant C. albicans is increasing at an alarming pace (4-6). Therefore, the need for effective anticandidal therapy is increasing, as the available drugs are still very restricted.Currently available therapies for candidiasis are based on antifungal drugs including azoles, echinocandins, and inhibitors of calcineurin, Hos2 deacetylase, and Hsp90 (7-10). Fluconazole (FCZ) is most widely used to treat candidiasis infections because of its high bioavailability and low toxicity (11-13). However, excessive and indiscriminate clinical use of FCZ has led to the emergence of multiple-drug-resistant (MDR) strains of C. albicans (5,14,15). Importantly, t...

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Fluconazole Assists Berberine To Kill Fluconazole-Resistant Candida albicans

Cited by 71 publications

References 50 publications

Sensitization of Candida albicans to terbinafine by berberine and berberrubine

Sensitization of Candida albicans to terbinafine by berberine and berberrubine

Berberine inhibits the MexXY‑OprM efflux pump to reverse imipenem resistance in a clinical carbapenem‑resistant Pseudomonas aeruginosa isolate in a planktonic state

Quercetin Sensitizes Fluconazole-Resistant Candida albicans To Induce Apoptotic Cell Death by Modulating Quorum Sensing

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