Potent synergic effect between ibuprofen and azoles on Candida resulting from blockade of efflux pumps as determined by FUN-1 staining and flow cytometry

Pina-Vaz, Cidália; Rodrigues, Acácio Gonçalves; Costa-de-Oliveira, Sofia; Ricardo, Elisabete; Mårdh, Per‐Anders

doi:10.1093/jac/dki264

Cited by 72 publications

(63 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[20,22]. Also, Ibuprofen show fungistatic activity at low concentrations and fungicidal activity at high concentrations [23]. In this study we tested the antifungal activity of three NSAIDs on different Candida Spp.…”

Section: Introductionmentioning

confidence: 99%

Effect of Some Non steroidal Anti-Inflammatory Drugs on Growth, Adherence and Mature Biofilms of Candida spp.

Ashraf¹,

Yousri²,

Taha³

et al. 2015

AJMR

View full text Add to dashboard Cite

Candida spp. are the most common cause of fungal diseases and the fourth commonest cause of nosocomial invasive infections which are considered in many cases as life threatening. Among Candida spp., C. albicans is the most common cause of many fungal diseases, but non-albicans spp. infections are in increase. Nonsteroidal anti-inflammatory drugs have previously been shown to have antifungal activity. In this study we determine the antifungal activity of the tested NSAIDs using agar well diffusion method, their effect on the dimorphic transition of C. albicans by testing their ability to form germ tube in the presence of human serum. Determining the effect of NSAIDs on the adherence to plastic surfaces and on the mature biofilms formed by the tested Candida spp.. The results indicated that Sodium Diclofenac showed lower MIC against C. albicans and C. glabrata while Ibuprofen had lower MIC against C. krusei. upon examining the effect of Diclofenac sodium, Ibuprofen and ketoprofen on biofilm formed on polyurethane segments by Scanning electron microscope (SEM), a damage to membranes of the tested species was observed. Sodium Diclofenac showed the highest inhibitory effect on the adherence (51.1-76.9% at MIC and 56.6-83.3% at 2XMIC) of C. albicans and C. glabrata but Ibuprofen showed a higher inhibitory effect against the adherence of C. krusei. For mature biofilms, the highest disruptive effect on mature biofilms formed by all tested Candida Spp. .06% at 2XMIC) was observed by Diclofenac sodium. Sodium Diclofenac inhibited dimorphic transition of C. albicans but a decrease in germ tube formation was shown by others. In conclusion, the tested drugs showed antifungal, anti-adherent and antibiofilm activity that make them useful in the treatment of fungal infection and the prevention of biofilm formation on the surface of medical devices.

show abstract

Section: Introductionmentioning

confidence: 99%

Effect of Some Non steroidal Anti-Inflammatory Drugs on Growth, Adherence and Mature Biofilms of Candida spp.

Ashraf¹,

Yousri²,

Taha³

et al. 2015

AJMR

View full text Add to dashboard Cite

show abstract

“…Therefore, the combination of CAS1 (4 g/ml) with AMB (0.25 g/ml), as well as that of CAS2 (8 g/ml) with VRC (4 g/ml) was used to inhibit the biofilm of A. fumigatus AF293. This combination was used as a model to observe the synergistic activity against Aspergillus biofilm by FUN-1 staining (8,15). With an Olympus FV-500 laser scanning confocal microscope, we observed that the amount of viable organisms in the A. fumigatus AF293 biofilm was significantly less when being treated with these drugs-CAS1 (4 g/ml) with AMB (0.25 g/ml) or CAS2 (8 g/ml) with VRC (4 g/ml) (see Fig.…”

mentioning

confidence: 99%

Interaction of the Echinocandin Caspofungin with Amphotericin B or Voriconazole against Aspergillus Biofilms In Vitro

Liu

Sun

et al. 2012

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Aspergillus biofilms were prepared from 22 strains of Aspergillus spp. via a 96-well plate-based method. Using a broth microdilution checkerboard technique with the XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] colorimetric assay, we demonstrated a synergistic antifungal activity against 18 of 22 Aspergillus biofilm strains with a combination of caspofungin and amphotericin B and against 13 of 22 strains with a combination of caspofungin and voriconazole. We did not observe antagonism.

show abstract

“…To reverse fungal FLC resistance, a putative chemosensitizer should be nontoxic in the absence of FLC but render a normally FLC-resistant strain more sensitive to FLC. Inhibitors of fungal ABC transporters include FK506 (30,42), enniatin (13), milbemycins (20), unnarmicins (48), isonitrile (56), disulfiram (44), ibuprofen (36), and quinazolinone derivatives (51). Such inhibitors, or chemosensitizers, may act indirectly on aspects of metabolism that affect efflux.…”

mentioning

confidence: 99%

“…FK506, for example, used in cancer chemotherapy as an immunosuppressant, may act both directly (since overexpression of Cdr1p significantly reduces susceptibility to FK506) (30,42) and indirectly (by effects on the calcineurin pathway) (2,12,46,47,49) to reverse resistance to FLC in fungi. Ibuprofen is a potent anti-inflammatory and analgesic drug, which at low concentrations inhibits azole efflux from C. albicans, and has been proposed for combination treatment of fungal infections with FLC (36).…”

mentioning

confidence: 99%

ABC Transporter Cdr1p Contributes More than Cdr2p Does to Fluconazole Efflux in Fluconazole-Resistant Candida albicans Clinical Isolates

Holmes

Lin

Niimi

et al. 2008

Antimicrob Agents Chemother

147

134

View full text Add to dashboard Cite

Fluconazole (FLC) remains the antifungal drug of choice for non-life-threatening Candida infections, but drug-resistant strains have been isolated during long-term therapy with azoles. Drug efflux, mediated by plasma membrane transporters, is a major resistance mechanism, and clinically significant resistance in Candida albicans is accompanied by increased transcription of the genes CDR1 and CDR2, encoding plasma membrane ABC-type transporters Cdr1p and Cdr2p. The relative importance of each transporter protein for efflux-mediated resistance in C. albicans, however, is unknown; neither the relative amounts of each polypeptide in resistant isolates nor their contributions to efflux function have been determined. We have exploited the pump-specific properties of two antibody preparations, and specific pump inhibitors, to determine the relative expression and functions of Cdr1p and Cdr2p in 18 clinical C. albicans isolates. The antibodies and inhibitors were standardized using recombinant Saccharomyces cerevisiae strains that hyper-express either protein in a host strain with a reduced endogenous pump background. In all 18 C. albicans strains, including 13 strains with reduced FLC susceptibilities, Cdr1p was present in greater amounts (2-to 20-fold) than Cdr2p. Compounds that inhibited Cdr1p-mediated function, but had no effect on Cdr2p efflux activity, significantly decreased the resistance to FLC of seven representative C. albicans isolates, whereas three other compounds that inhibited both pumps did not cause increased chemosensitization of these strains to FLC. We conclude that Cdr1p expression makes a greater functional contribution than does Cdr2p to FLC resistance in C. albicans.Factors identified as affecting the susceptibility of Candida albicans to azole antifungal drugs such as fluconazole (FLC) include overexpression or mutation of the drug target 14␣ lanosterol demethylase, mutations in other enzymes of the ergosterol pathway and increased expression of drug efflux pumps (reviewed in references 4, 40, and 53). Mediators of azole efflux from C. albicans include the major facilitator superfamily pumps Mdr1p (28) and Flu1p (1) and the ATPbinding cassette (ABC) transporters Cdr1p and Cdr2p (4, 52). Although FLC resistance clearly can be multifactorial, highlevel, clinically relevant resistance (MIC Ն 64 g ml Ϫ1 ) is most often associated with increased expression of mRNAs from the ABC genes CDR1 and CDR2 (3, 34, 37, 38). Analysis of resistance in clinical isolates has, to date, focused almost exclusively on measuring gene transcription, initially by Northern analysis (22,41,53), and more recently by transcript profiling and quantitative reverse transcription-PCR (16,34,38,55) and the use of reporter genes (24). However, the ability to compare the amounts of expressed Cdr polypeptides and, more importantly, the efflux activities of Cdr1p and Cdr2p, is crucial if the contribution of each pump protein to drug efflux function in clinical resistance is to be determined. Unfortunately, proteomic approaches using...

show abstract

Potent synergic effect between ibuprofen and azoles on Candida resulting from blockade of efflux pumps as determined by FUN-1 staining and flow cytometry

Cited by 72 publications

References 24 publications

Effect of Some Non steroidal Anti-Inflammatory Drugs on Growth, Adherence and Mature Biofilms of <i>Candida spp</i><i>.</i>

Effect of Some Non steroidal Anti-Inflammatory Drugs on Growth, Adherence and Mature Biofilms of <i>Candida spp</i><i>.</i>

Interaction of the Echinocandin Caspofungin with Amphotericin B or Voriconazole against Aspergillus Biofilms In Vitro

ABC Transporter Cdr1p Contributes More than Cdr2p Does to Fluconazole Efflux in Fluconazole-Resistant Candida albicans Clinical Isolates

Contact Info

Product

Resources

About