Proposal for a screening protocol for Candida auris colonization.

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast which can cause severe infection in hospitalized patients. Since its first detection in 2009, C. auris has spread globally. The control and elimination of this pathogen in a hospital setting is particularly challenging because of its ability to form biofilms, allowing for long-term patient colonization and persistence in the environment. Identification of C. auris from cultures is difficult due to the morphologic similarities to other yeasts, its slow growth, and the low culture sensitivity when using standard agars and temperatures. AIM: We have developed a screening protocol for C. auris colonization using an in-house-developed polymerase chain reaction (PCR), combined with confirmatory culture in optimized conditions. METHODS: C. auris-specific primers and probe were developed, targeting the internal transcribed spacer (ITS) region, and specificity was confirmed in silico using the BLAST tool. The PCR was validated using a panel of 12 C. auris isolates and 103 isolates from 22 other Candida species and was shown to be 100% accurate. The limit of detection of the assay was determined at approximately four cells per PCR. FINDINGS: C. auris screening was introduced on February 15th, 2023, and was used for patients who had been admitted to a healthcare facility abroad in the two months prior to admission to our hospital. The screening protocol included swabs from nose, throat, rectum, axilla, and groin. In the first eight months, 199 patients were screened and seven were found positive (4%). CONCLUSION: Our proposed screening protocol may contribute to control C. auris in hospitals.

Plastic pollution as a novel reservoir for the environmental survival of the drug resistant fungal pathogen Candida auris.

The WHO recently classified Candida auris as a fungal pathogen of "critical concern". Evidence suggests that C. auris emerged from the natural environment, yet the ability of this pathogenic yeast to survive in the natural environment is still poorly understood. The aim of this study, therefore, was to quantify the persistence of C. auris in simulated environmental matrices and explore the role of plastic pollution for facilitating survival and potential transfer of C. auris. Multi-drug resistant strains of C. auris persisted for over 30 days in river water or seawater, either planktonically, or in biofilms colonising high-density polyethylene (HDPE) or glass. C. auris could be transferred from plastic beads onto simulated beach sand, particularly when the sand was wet. Importantly, all C. auris cells recovered from plastics retained their pathogenicity; therefore, plastic pollution could play a significant role in the widescale environmental dissemination of this recently emerged pathogen.

Flipping and other astonishing transporter dance moves in fungal drug resistance.

In all domains of life, transmembrane proteins from the ATP-binding cassette (ABC) transporter family drive the translocation of diverse substances across lipid bilayers. In pathogenic fungi, the ABC transporters of the pleiotropic drug resistance (PDR) subfamily confer antibiotic resistance and so are of interest as therapeutic targets. They also drive the quest for understanding how ABC transporters can generally accommodate such a wide range of substrates. The Pdr5 transporter from baker's yeast is representative of the PDR group and, ever since its discovery more than 30 years ago, has been the subject of extensive functional analyses. A new perspective of these studies has been recently provided in the framework of the first electron cryo-microscopy structures of Pdr5, as well as emergent applications of machine learning in the field. Taken together, the old and the new developments have been used to propose a mechanism for the transport process in PDR proteins. This mechanism involves a "flippase" step that moves the substrates from one leaflet of the bilayer to the other, as a central element of cellular efflux.

A comparative study of in-vitro and in-silico anti-candidal activity and GC-MS profiles of snow mountain garlic vs. normal garlic.

AIM: The study aimed to profile the volatile phytocomposition of snow mountain garlic (SMG) compared to normal garlic and investigate the anti-Candida efficacy against clinically relevant multi-drug resistant isolates of Candida species. METHODS AND RESULTS: Herein, SMG has shown significantly superior fungicidal power at 2x-MIC dose against C. albicans and C. glabrata in killing kinetic evaluation unlike the fungistatic effect of normal garlic. GC-MS headspace-based profiling of SMG showed 5 unique volatile compounds and a 5-fold higher content of saponins than normal garlic. In an in-silico analysis, cholesta-4,6-dien-3-ol,(3-beta) was uniquely identified in SMG as a potential inhibitor with high binding affinity to the active site of exo-1,3-betaglucan synthase, an established anti-candida drug target crucial for the biofilm matrix formation, thus suggesting a plausible anti-Candida mechanism. CONCLUSION: The in-vitro and in-silico studies have demonstrated the Candida-cidal and anti-biofilm activities of SMG, distinguishing it from the Candida-static efficacy of normal garlic. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report that identifies several phytochemical signatures of SMG along with a potential anti-Candida compound, that is cholesta-4,6-dien-3-ol,(3-beta)-, which appears worthy of detailed studies in the future to explore the utility of SMG as a fungal phytotherapy agent, especially against drug-resistant Candida sp.

Eficácia antimicrobiana da terapia fotodinâmica no tratamento da candidíase oral em pessoas vivendo com HIV/Aids / Antimicrobial efficacy of photodynamic therapy on the treatment of oral candidiasis in people living with HIV/Aids / Eficacia antimicrobiana de la terapia fotodinámica en el tratamiento de la candidiasis bucal en personas viviendo con VIH/Sida

Objetivo: avaliar a eficácia antimicrobiana da terapia fotodinâmica no tratamento da candidíase oral em pessoas vivendo com HIV/aids. Método: estudo experimental, qualitativo e descritivo com 18 pessoas vivendo com HIV/aids que manifestavam a candidíase oral, maiores de 18 anos, que estavam em tratamento no Hospital Universitário Gaffrée e Guinle. Este grupo subdividiu-se em um grupo controle, composto por sete pessoas, que recebeu tratamento com a terapia fotodinâmica e antifúngicos, e um grupo experimental, com 11, que recebeu apenas a terapia fotodinâmica. A evolução do tratamento de cada participante foi acompanhada por registros fotográficos em duas consultas, inicial e final. Esta pesquisa foi aprovada pelo Comitê de Ética em Pesquisa do hospital, parecer número 2.431.107. Resultados: a maioria dos participantes apresentou melhora clínica, ainda que discreta, e em apenas um houve piora clínica. Conclusão: a terapia fotodinâmica antimicrobiana pode ser eficaz no tratamento da candidíase oral em pessoas vivendo com HIV/Aids

Objective: evaluate the antimicrobial efficacy of photodynamic therapy in the treatment of oral candidiasis in people living with HIV/ aids. Method: experimental, qualitative and descriptive study with 18 people living with HIV/aids who presented oral candidiasis, over 18 years of age, who were being treated at the Gaffrée and Guinle University Hospital. This group was subdivided into a control group, composed of seven people, who received treatment with photodynamic and antifungal therapy, and an experimental group, with 11, who received only the photodynamic therapy. The evolution of the treatment of each participant was followed by photographic registers in two appointments, initial and final. This research was approved by the Research Ethics Committee from the hospital, dictum number 2.431.107. Results: most of the participants showed clinical improvement, albeit discrete, and in only one there was clinical worsening. Conclusion: antimicrobial photodynamic therapy may be effective in the treatment of oral candidiasis in people living with HIV/Aids

Objetivo: evaluar la eficacia antimicrobiana de la terapia fotodinámica en el tratamiento de la candidiasis bucal en personas que viven con VIH/sida. Método: estudio experimental, cualitativo y descriptivo con 18 personas viviendo con VIH/sida que manifestaban la candidiasis bucal, mayores de 18 años, que estaban en tratamiento en el Hospital Universitario Gaffrée y Guinle. Este grupo se subdividió en grupo control, compuesto por siete personas, que recibió tratamiento con la terapia fotodinámica y antifúngicos, y un grupo experimental, con 11, que recibió sólo la terapia fotodinámica. La evolución del tratamiento de cada participante fue acompañada por registros fotográficos en dos consultas, inicial y final. La investigación fue aprobada por el Comité de Ética en Investigación del lugar, dictamen número 2.431.107. Resultados: la mayoría de los participantes presentó mejoría clínica, aunque discreta, y en apenas uno hubo empeoramiento clínico. Conclusión: la terapia fotodinámica antimicrobiana puede ser eficaz en el tratamiento de la candidiasis bucal en personas que viven con el VIH/Sida

Optogenetic Repressors of Gene Expression in Yeasts Using Light-Controlled Nuclear Localization.

INTRODUCTION: Controlling gene expression is a fundamental goal of basic and synthetic biology because it allows insight into cellular function and control of cellular activity. We explored the possibility of generating an optogenetic repressor of gene expression in the model organism Saccharomyces cerevisiae by using light to control the nuclear localization of nuclease-dead Cas9, dCas9. METHODS: The dCas9 protein acts as a repressor for a gene of interest when localized to the nucleus in the presence of an appropriate guide RNA (sgRNA). We engineered dCas9, the mammalian transcriptional repressor Mxi1, and an optogenetic tool to control nuclear localization (LINuS) as parts in an existing yeast optogenetic toolkit. This allowed expression cassettes containing novel dCas9 repressor configurations and guide RNAs to be rapidly constructed and integrated into yeast. RESULTS: Our library of repressors displays a range of basal repression without the need for inducers or promoter modification. Populations of cells containing these repressors can be combined to generate a heterogeneous population of yeast with a 100-fold expression range. We find that repression can be dialed modestly in a light dose- and intensity-dependent manner. We used this library to repress expression of the lanosterol 14-alpha-demethylase Erg11, generating yeast with a range of sensitivity to the important antifungal drug fluconazole. CONCLUSIONS: This toolkit will be useful for spatiotemporal perturbation of gene expression in Saccharomyces cerevisiae. Additionally, we believe that the simplicity of our scheme will allow these repressors to be easily modified to control gene expression in medically relevant fungi, such as pathogenic yeasts.

Molecular typing and in vitro resistance of Cryptococcus neoformans clinical isolates obtained in Germany between 2011 and 2017.

Cryptococcosis is a fungal infection of the central nervous system predominantly caused by Cryptococcus neoformans in immunocompromised patients. In several countries worldwide, up to 50% of isolates show in vitro resistance to clinically used antifungals including fluconazole. No prospective data on susceptibility to antifungal drugs are available for Germany. In this study, we characterised all C. neoformans isolates collected from individual patients' samples at the German reference laboratory for cryptococcosis 2011 and 2017 (n = 133) by multi-locus sequence typing and phenotypic drug susceptibility testing. We identified serotype A/genotype VNI isolates belonging to clonal complexes previously described from Europe, Africa, Asia and South America as the most prevalent agents of cryptococcosis in Germany. Overall, we observed minimal inhibitory concentrations (MICs) above the epidemiological cut-offs (ECVs) in 1.6% of isolates regarding fluconazole and 2.3% of isolates regarding 5-flucytosine. Here, two C. neoformans var. grubii isolates displayed decreased drug susceptibility to fluconazole, one of them additionally to 5-flucytosine. We also found 5-flucytosine MICs above the ECV for two C. neoformans var. neoformans isolates. We identified a novel mutation in the ERG11 gene which might be associated with the elevated fluconazole MIC in one of the isolates. The clinical importance of the detected in vitro resistance is documented by patient histories showing relapsed infection or primary fatal disease. Of note, sertraline demonstrated antifungal activity comparable to previous reports. Systematic collection of susceptibility data in combination with molecular typing of C. neoformans is important to comprehensively assess the spread of isolates and to understand their drug resistance patterns.

Minimum Inhibitory Concentration Distribution of Fluconazole against Cryptococcus Species and the Fluconazole Exposure Prediction Model.

BACKGROUND: Fluconazole is lifesaving for treatment and prevention of cryptococcosis; however, optimal dosing is unknown. Initial fluconazole doses of 100mg to 2000mg/day have been used. Prevalence of fluconazole non-susceptible Cryptococcus is increasing over time, risking the efficacy of long-established standard dosing. Based on current minimum inhibitory concentration (MIC) distribution, we modeled fluconazole concentration and area under the curve (AUC) relative to MIC to propose a rational fluconazole dosing strategy. METHODS: First, we conducted a systematic review using MEDLINE database for reports of fluconazole MIC distribution against clinical Cryptococcus isolates. Second, we utilized fluconazole concentrations from 92 Ugandans who received fluconazole 800mg/day coupled with fluconazole's known pharmacokinetics to predict plasma fluconazole concentrations for doses ranging from 100mg to 2000mg via linear regression. Third, the fluconazole AUC above MIC ratio were calculated using Monte Carlo simulation and using the MIC distribution elucidated during the systemic review. RESULTS: We summarized 21 studies with 11,049 clinical Cryptococcus isolates. MICs were normally distributed with geometric mean of 3.4 µg/mL, median (MIC50) of 4 µg/mL, and 90th percentile (MIC90) of 16 µg/mL. The median MIC50 trended upwards from 4 µg/mL in 2000-2012 to 8 µg/mL in 2014-2018. Predicted sub-therapeutic fluconazole concentrations (below MIC) would occur in 40% with 100mg, 21% with 200mg, and 9% with 400mg. AUC/MIC ratio >100 would occur in 53% for 400mg, 74% for 800mg, 83% for 1200mg, and 88% for 1600mg. CONCLUSIONS: Currently recommended fluconazole doses may be inadequate for cryptococcosis. Further clinical studies are needed for rational fluconazole dose selection.

The fungal cell wall as a target for the development of new antifungal therapies.

In the past three decades invasive mycoses have globally emerged as a persistent source of healthcare-associated infections. The cell wall surrounding the fungal cell opposes the turgor pressure that otherwise could produce cell lysis. Thus, the cell wall is essential for maintaining fungal cell shape and integrity. Given that this structure is absent in host mammalian cells, it stands as an important target when developing selective compounds for the treatment of fungal infections. Consequently, treatment with echinocandins, a family of antifungal agents that specifically inhibits the biosynthesis of cell wall (1-3)ß-D-glucan, has been established as an alternative and effective antifungal therapy. However, the existence of many pathogenic fungi resistant to single or multiple antifungal families, together with the limited arsenal of available antifungal compounds, critically affects the effectiveness of treatments against these life-threatening infections. Thus, new antifungal therapies are required. Here we review the fungal cell wall and its relevance in biotechnology as a target for the development of new antifungal compounds, disclosing the most promising cell wall inhibitors that are currently in experimental or clinical development for the treatment of some invasive mycoses.

Epidemiology of Candidemia at a University Hospital in Colombia, 2008-2014 / Epidemiología de los casos de candidemia en un hospital universitario en Colombia, 2008-2014

Introducción: Candida spp. es una levadura comensal de la microbiota humana. Por características del hospedero, las infecciones del torrente sanguíneo pueden aparecer y causar una gran morbimortalidad. Métodos: Estudio restrospectivo transversal analítico de los cultivos positivos para Candida spp. entre 2008 y 2014 en un hospital universitario en Bogotá, Colombia. Se evaluaron las características clínicas y microbiológicas presentes previo a la toma de la primera muestra de sangre positiva y se determinaron asociaciones con infecciones por especies no C. albicans (NCA). Resultados: Se incluyeron 123 casos de candidemia. C. albicans fue la especie más aislada (42 %). Sin embargo, las especies NCA como grupo fueron observadas más frecuentemente. Más del 70 % de los casos presentaron manejo en la unidad de cuidado intensivo, con una mediana de estancia de 14 días previo a la primera muestra de sangre positiva. Se detectaron numerosas características médicas; sin embargo, ninguna estuvo asociada con candidemia por especies NCA. Se observó resistencia a por lo menos un antifúngico en el 29 % de los casos, aunque en una muestra reducida de pruebas de sensibilidad. Conclusiones: Nuestros resultados sustentan el viraje mundial hacia la candidemia por especies NCA; pero no encontramos asociaciones clínicas en este grupo. Debe dársele prioridad a la identificación de factores de riesgo y a la optimización de los puntajes de predicción, que permitan identificar pacientes en riesgo que se beneficien de terapia preventiva.

Introduction: Candida species are commensal yeasts of the human microbiota. However, due to several host's conditions, bloodstream infections may arise causing high morbimortality. Methods: Retrospective cross-sectional analytical study of positive blood cultures for Candida spp. between 2008'2014 at a university hospital in Bogotá. Colombia. We evaluated clinical and microbiological characteristics prior to the first positive blood sample was obtained and determined associations with non'C. albicans (NCA) species infections. Results: We included 123 candidemia cases. C. albicans was the most frequently isolated species (42%). However; NCA species as a group were observed more often. Over 70% of cases were managed at the ICU, with a median stay of 14 days. Several medical factors were frequently observed, however none appeared to be associated with NCA species candidemia. Resistance to at least one antifungal agent was observed in 29% of cases, although a reduced sample of susceptibility tests was available. Conclusions: Our results support a worldwide shift towards NCA candidemia. However, clinical features were not associated with NCA infections. The identification of risk factors and the improvement of prediction scores must be prioritized, in order to identify' patients at high risk who may benefit of pre-emptive therapy.

Atomic modelling and systematic mutagenesis identify residues in multiple drug binding sites that are essential for drug resistance in the major Candida transporter Cdr1.

The ABC (ATP-Binding Cassette) transporter Cdr1 (Candida drug resistance 1) protein (Cdr1p) of Candida albicans, shows promiscuity towards the substrate it exports and plays a major role in antifungal resistance. It has two transmembrane domains (TMDs) comprising of six transmembrane helices (TMH) that envisage and confer the substrate specificity and two nucleotide binding domains (NBDs), interconnected by extracellular loops (ECLs) and intracellular loops (ICLs) Cdr1p. This study explores the diverse substrate specificity spectrum to get a deeper insight into the structural and functional features of Cdr1p. By screening with the variety of compounds towards an in-house TMH 252 mutant library of Cdr1p, we establish new substrates of Cdr1p. The localization of substrate-susceptible mutants in an ABCG5/G8 homology model highlights the common and specific binding pockets inside the membrane domain, where rhodamines and tetrazoliums mainly engage the N-moiety of Cdr1p, binding between TMH 2, 11 and surrounded by TMH 1, 5. Whereas, tin chlorides involve both N and C moieties located at the interface of TMH 2, 11, 1 and 5. Further, screening of the in house TMH mutant library of Cdr1p displays the TMH12 interaction with tetrazolium chloride, trimethyltin chloride and a Ca2+ ionophore, A23187. In silico localization reveals a binding site at the TMH 12, 9 and 10 interface, which is widely exposed to the lipid interface. Together, for the first time, our study shows the molecular localization of Cdr1p substrates-binding sites and demonstrates the participation of TMH12 in a peripheral drug binding site.

Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation.

Resistance of Candida albicans Biofilms to Drugs and the Host Immune System.

BACKGROUND: Candida albicans is a commensal fungus that resides on mucosal surfaces and in the gastrointestinal and genitourinary tracts in humans. However, it can cause an infection when the immune system of the host is impaired or if a niche becomes available. Many C. albicans infections are due to the organism's ability to form a biofilm on implanted medical devices. A biofilm represents an optimal medium for the growth of C. albicans as it allows cells to be enclosed by a self-produced extracellular matrix (ECM). OBJECTIVES: The present work investigated certain aspects of the resistance of C. albicans biofilms to drugs and the host immune system. RESULTS: An ECM was found to provide the infrastructure for biofilm formation, prevent disaggregation, and shield encapsulated C. albicans cells from antifungal drugs and the host's immune system. By influencing FKS1 and upregulating multiple glucan modification genes, ß-1, 3-glucan, an important component of ECM, was shown to be responsible for many of the biofilm's drug-resistant properties. On being engulfed by ECM, the fungal cell was found to switch from glycolysis to gluconeogenesis. Resembling the cellular response to starvation, this was followed by the activation of the glyoxylate cycle that allowed the use of simple molecules as energy sources. CONCLUSION: Mature biofilms were found to be much more resistant to antifungal agents and the host immune system than free cells. The factors responsible for high resistance included the complex architecture of biofilms, ECM, increased expression of drug efflux pumps, and metabolic plasticity.

Local, systemic, demographic, and health-related factors influencing pathogenic yeast spectrum and antifungal drug administration frequency in oral candidiasis: a retrospective study.

OBJECTIVES: In order to identify oral candidiasis patients being at risk of carrying potentially drug-resistant Candida, the aim of the study was to detect local, systemic, demographic, and health-related factors influencing (I) yeast spectrum composition and (II) antifungal administration frequency. Additionally, the aim was to investigate (III) species shift occurrence. MATERIALS AND METHODS: Data from 798 patients (496 females, 302 males; mean age 59.7) with oral candidiasis diagnosed based on positive clinical and microbial findings (species identification and CFU count) between 2006 and 2011 were retrospectively analyzed using Pearson's chi(2) test and regression analysis. RESULTS: Among 958 isolates, Candida albicans was the most frequently detected (76.8 %). Also, species intrinsically resistant to azoles were frequently isolated (15.8 and 17.7 % of isolates and patients). (I) Infections only caused by C. albicans were significantly associated with the use of inhalation steroids (p = 0.001) and antibiotics (p = 0.04), super-infection of lichen planus (p = 0.002), and the absence of removable dentures (p < 0.001). (II) Anti-mycotics were significantly more frequently administered in patients using inhalation steroids (p = 0.001), suffering from asthma/COPD, or smoking heavily (p = 0.003) and if C. albicans and non-albicans species were detected together (p = 0.001). (III) Pathogen composition did not change over time within the examined period (p = 0.239). CONCLUSIONS: Different variables enhance the presence of certain Candida and the antifungal prescription frequency. No species shift was evident. CLINICAL RELEVANCE: The major pathogen in oral candidiasis remains C. albicans. Nevertheless, therapeutic problems may be caused by the frequent presence of species intrinsically resistant to azoles, especially in patients wearing dentures.

Resistencia de levaduras del género Candida al fluconazol / Candida yeast´s resistance to fluconazol

Las infecciones por levaduras del género Candida sp. son cada vez más prevalentes en pacientes hospitalizados, especialmente en grupos de mayor riesgo como pueden ser pacientes con neoplasia hematológica bajo tratamiento de quimioterapia y en cuidados intensivos. La resistencia de Candida sp. representa un reto terapéutico que deja un menor número de posibilidades para el tratamiento de estas infecciones que se caracterizan, a su vez, por una alta morbimortalidad. Esta revisión describe los mecanismos de resistencia de Candida sp. a fluconazol y los factores de riesgo para la adquisición de éstos.

Yeast infections of the genus Candida sp are becoming more prevalent in hospitalized patients, especially in high risk groups such as patients with hematologic malignancy undergoing chemotherapy and in intensive care units. Candida sp's resistance represents a therapeutic challenge that leaves fewer opportunities for the treatment of these infections which are characterized by high morbidity and mortality. This review describes Candida sp's resistance mechanisms to fluconazole and the risk factors for their acquisition.

ATP-binding-cassette transporters and fluconazole-resistance of clinical Candida albicans strains / 第二军医大学学报

Objective: To explore the relationship between CDR1 and CDR2 expression and fluconazole-resistance in clinical Candida albicans strains, so as to explore the mechanism of drug-resistance in Candida albicans. Methods: The minimal inhibitory concentrations (MICs) of clinical Candida albicans strains to fluconazole were determined by broth microdilution method. The total RNA of fluconazole-susceptible and fluconazole-resistant Candida albicans strains were extracted, and the expression of the CDR1 and CDR2 genes was examined by real-time RT-PCR. The efflux of Rhodamine 6G was determined in the strains highly expressing CDR1 and CDR2 genes. Results: The incidences of CDR1 and (or) CDR2 overexpression in fluconazole-resistant strains were significantly higher than those in the fluconazole-sensitive stains. The efflux of Rhodamine 6G was significantly increased in the fluconazole-resistant strains when glucose was added, and overexpression of CDR1 and CDR2 were observed in theses strains. Some resistant strains showed no overexpression of CDR1 and CDR2. Conclusion: Fluconazole-resistance in clinical Candida albicans strains is related to the overexpression of ABC transporter proteins. Overexpression of ABC transporters can increase the efflux of drugs and therefore lead to drug-resistance. Other mechanisms may also participate in the development of drug resistance in the clinical Candida albicans strains.