Azole-resistant<i>Candida albicans</i>from a wild Brazilian porcupine (<i>Coendou prehensilis</i>): a sign of an environmental imbalance?

Castelo-Branco, Débora de Souza Collares Maia; Brilhante, Raimunda Sâmia Nogueira; Paiva, Manoel A. N.; Teixeira, Carlos Eduardo Cordeiro; Caetano, Érica Pacheco; Ribeiro, Jefferson Pereira; Cordeiro, Rossana de Aguiar; Sidrim, J. J. C.; Monteiro, André Jalles; Rocha, Marcos Fábio Gadelha

doi:10.3109/13693786.2012.752878

Cited by 33 publications

(43 citation statements)

References 34 publications

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“…This study firstly demonstrates that the combinations of FLZ or VOR with HAL and/or PTZ increased the susceptibility of M. furfur and M. pachydermatis to azoles, suggesting that the drug efflux pumps might be involved in the defence mechanism of Malassezia yeasts against these drugs. Indeed HAL, PTZ and CYS inhibit, directly or indirectly, the activities of the fungal membrane efflux pumps, possibly increasing the susceptibility to antifungal drugs or to reverse azole resistance, as demonstrated for Candida spp …”

Section: Discussionmentioning

confidence: 95%

The role of drug efflux pumps in Malassezia pachydermatis and Malassezia furfur defence against azoles

Iatta

Puttilli

Immediato

et al. 2016

Mycoses

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This study aims to evaluate the effect of efflux pump modulators (EPMs) on the minimal inhibitory concentration (MIC) of fluconazole (FLZ) and voriconazole (VOR) in Malassezia furfur and Malassezia pachydermatis. The in vitro efficacy of azoles, in combination with EPMs (ie haloperidol-HAL, promethazine-PTZ and cyclosporine A-CYS), against 21 M. furfur from bloodstream infection patients and 14 M. pachydermatis from the skin of dogs with dermatitis, was assessed using a broth microdilution chequerboard analysis. Data were analysed using the model-fractional inhibitory concentration index (FICI) method. The MIC of FLZ and VOR of Malassezia spp. decreased in the presence of sub-inhibitory concentrations of HAL and/or PTZ. The synergic effect was observed only in strains with FLZ MIC≥128 μg/mL for M. furfur, FLZ MIC≥64 μg/mL for M. pachydermatis and VOR MIC≥4 μg/mL in both Malassezia spp. These results suggest that the drug efflux pumps are involved as defence mechanisms to azole drugs in Malassezia yeast. The synergism might be related to an increased expression of efflux pump genes, eventually resulting in azole resistance phenomena. Finally, the above FLZ and VOR MIC values might be considered the cut-off to discriminate susceptible and resistant strains.

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Section: Discussionmentioning

confidence: 95%

The role of drug efflux pumps in Malassezia pachydermatis and Malassezia furfur defence against azoles

Iatta

Puttilli

Immediato

et al. 2016

Mycoses

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“…It has also been reported that azole‐resistant Candida isolates have been found in lake water and in a porcupine in Brazil. The resistance were mediated by efflux pumps . Whether these findings have implications for human infection is unknown as our study was not designed to reveal associations between agricultural azoles and candidaemia or Candida resistance.…”

Section: Discussionmentioning

confidence: 99%

Differences in epidemiology of candidaemia in the Nordic countries – what is to blame?

Hesstvedt

Arendrup

Poikonen

et al. 2016

Mycoses

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National data from Denmark, Finland, Norway and Sweden demonstrate remarkable differences in candidaemia epidemiology. Only Denmark has reported a high incidence of 10 per 100 000 inhabitants and a species shift towards increased C. glabrata candidaemias. The reasons for this development remain unclear. The aim of this study was to explore possible contributing factors for the differences in Candida epidemiology in the Nordic countries. We used public data from 2011 from Denmark, Finland, Norway and Sweden on epidemiology, demographics, health facilities, predisposing risk factors, consumption of antimicrobial drugs and fungicides in agricultural industry. Only the prevalence of haematological malignancies (P < 0.001) was significantly higher in Denmark compared to the other Nordic countries. The antibacterial drug use of metronidazole, piperacillin-tazobactam, ciprofloxacin, colistin and carbapenems, and antifungal use of fluconazole in humans (P < 0.001), were significantly higher in Denmark compared to the other Nordic countries (all P < 0.001). Our findings suggest haematological malignancy, the use of certain antibacterial drugs and azoles in humans as possible contributing factors for the differences in Candida epidemiology. However, our results should be interpreted with caution due to the lack of long-term, case-specific data. Further studies are needed.

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“…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). Therefore, the need for effective anticandidal therapy is increasing, as the available drugs are still very restricted.…”

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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Azole-resistantCandida albicansfrom a wild Brazilian porcupine (Coendou prehensilis): a sign of an environmental imbalance?

Cited by 33 publications

References 34 publications

The role of drug efflux pumps in Malassezia pachydermatis and Malassezia furfur defence against azoles

The role of drug efflux pumps in Malassezia pachydermatis and Malassezia furfur defence against azoles

Differences in epidemiology of candidaemia in the Nordic countries – what is to blame?

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

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