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Background: I Infections due to Candida spp. have increased dramatically in recent years through a rising number of predisposing factors and immunocompromised hosts. Although Candida albicans is the most prevalent and important causative agent of Candida infections, the importance of C. parapsilosis, C. tropicalis, C. krusei, C. glabrata, C. guilliermondii and C. kefyr have increased significantly as they tend to be more resistant to antifungal agents. Therefore, it is critical that infecting Candida spp. be identified and considered. Furthermore, clinical laboratories may need to expand their yeast identification capabilities in order to facilitate rapid identification of clinical yeast isolates. Methods: In a discroptive – analytic study, the patients suspected of candidiasis were sampled. Direct examination and culture was carried out for all specimens. The isolated yeast colonies were then identified using various different tests such as culture on corn mealagar tween-80, CHROMagar Candida, and assimilation test by API 20C AUX kit. Results: In the present study, 304 yeast colonies were isolated from referral patients to mycology laboratory of 304 isolated colonies 204 were identified as C. albicans and 100 were identified as non albicans candida as follow 35% C. parapsilosis, 32% C. tropicalis, 8% C. glabrata, 8% C. kefyer, 6% C. krusei, 3% C. guilliermondii, 3% C. famata, 3% C. lusitaniae, 1% C. zeilanoides and 1% C. homicola. C. parapsilosis was the most frequent species. The result showed that clinical specimens were obtained from various infected sites of body and nail samples (59 cases) were found to be the most frequent among those specimens. Conclusion: In conclusion, our results suggest that no single phenotypic test has proven to be highly effective for definitive identification. Moreover since these organisms can vary greatly in their susceptibility to the current antifungal agent and causing significant patient management problem therefore evaluation of susceptibility of these isolates against antifungal drugs is need to be investigated.

Background: Mucormycosis is an acute and invasive fungal infection with a high mortality rate. Mucorales are less sensitive than other types of fungi to most antifungal agents. Amphotericin B (AMB) is one treatment option for this infection, but in recent studies, the antifungal activity of statins against Mucorales was shown. Therefore, therapy that combines AMB with these agents may have better effects in management of patients with mucormycosis. We evaluated the in vitro activity of AMB alone and in combination with statins, against Mucorales., Methods: Susceptibility profiles of AMB alone and in combination with two statins, atorvastatin (ATO) and lovastatin (LOV) determined against clinical (n: 15) and environmental (n: 5) Rhizopus oryzae isolates, obtained between Jan 2009 and Oct 2016 from patients with uncontrolled diabetes mellitus and cancer referred to the Department of Parasitology and Medical Mycology of Tehran University of Medical Sciences, Tehran, Iran. It was performed by microdilution method, based on the Clinical and Laboratory Standard Institute (CLSI) M38-A2 guideline., Results: All clinical and environmental isolates were susceptible to AMB (MIC≤1 μg/mL). The results of the interactions between AMB and the two statins were positive. The AMB-ATO (GM: 0.13 μg/Ml) combination produced greater activity than the AMB-LOV (GM: 0.26 μg/mL) combination. AMB, in combination with ATO and LOV, reacts positively against clinical and environmental R. oryzae isolates., Conclusion: This combination strategy may lead to more effective treatment of mucormycosis and fewer side effects using low dose of AMB., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Background: Candiduria in hospitalized patients may represent contamination, colonization, or urinary tract infections. On the other hand, candidemia and upper urinary tract infection could be the complications of candiduria. The aim of this study was to determine candiduria in hospitalized patients and identify isolated Candida species by conventional and molecular methods., Methods: This cross-sectional study was conducted on hospitalized patients in Imam Khomeini and Mostafa Khomeini hospitals in Ilam, western Iran from Jan to Dec 2016. Urine samples of hospitalized patients were collected during a period of 4 months for diagnosis of candiduria. Primary identification was done by conventional methods. PCR profile was carried out using phenol-chloroform method and confirmed using restriction fragment length polymorphism (PCR-RFLP) technique by MspI restriction enzyme., Results: Candiduria was diagnosed in 18 (9.2%) cases from a total of 195 patients. Isolated yeasts were identified as C. albicans (n: 13), C. glabrata (n: 5), and C. parapsilosis (n: 1) in the one case both C. albicans and C. glabrata were isolated from a urine sample., Conclusion: Candida urinary tract infection is becoming increasingly common in hospitalized patients but, differentiation fungal colonization from infection and identification of etiologic agents for optimal treatment is necessary., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Introduction: Candiduria is common in the hospitalized patients. This study aimed to quantify interleukin (IL)-17 and IL-22 levels in urine of candiduric patients., Materials and Methods: A case-control study was conducted on inpatients at Hashemi Nejad Kidney Center. Thirty-four patients were identified with Candida species in their urine samples (> 103 colony-forming units per milliliter and presence of Candida species only). Urine samples with concomitant infections were excluded. Thirty-four patients with negative direct examination and culture were included as the control patients. Interleulin-17 and IL-22 levels were measured in the lyophilized and nonlyophilized urine. The relevant cytokine titers of the two groups were compared, and the association of cytokine elevation and candiduria was investigated., Results: The majority of the candiduric patients were from the intensive care and urology units of women. Only 4 patients (11.7%) manifested fever and dysuria. Massive leukocyturia was observed in 4 patients. Candida glabrata was the most commonly isolated species (44%). Levels of the urine IL-17 and IL-22 were significantly elevated in the candiduric patients, when compared to the noncandiduric controls. While an increased IL-17 level was significantly associated with candiduria (odds ratio, 1.09; 95% confidence interval, 1.003 to 1.17; P = .04), an increased IL-22 level was not. The results showed that lyophilized urine samples maximized the detection power of urinary cytokines., Conclusions: Our results indicated that direct examination, fungal urine culture, and investigation of urine IL-17 and IL-22 levels are useful tools for diagnosis of Candida urinary tract infection.

Purpose: Introducing the effect of RNAi in fungi to downregulate essential genes has made it a powerful tool to investigate gene function, with potential strategies for novel disease treatments. Thus, this study is an endeavor to delve into the silencing potentials of siRNA on cyp51A and MDR1 in voriconazole-resistant Aspergillus flavus as the target genes. Methods: In this study, we designed three cyp51A-specific siRNAs and three MDR1-specific siRNAs and after the co-transfection of siRNA into Aspergillus flavus, using lipofectamine, we investigated the effect of different siRNA concentrations (5, 15, 25, 50nM) on cyp51A and MDR1 expressions by qRT-PCR. Finally, the Minimum Inhibitory Concentrations (MICs) of voriconazole for isolates were determined by broth dilution method. Results: Cyp51A siRNA induced 9, 22, 33, 40-fold reductions in cyp51A mRNA expres-sion in a voriconazole-resistant strain following the treatment of the cells with concentrations of 5, 15, 25, 50nM siRNA, respectively. Identically, the same procedure was applied to MDR1, even though it induced 2, 3, 4, 10-fold reductions. The results demonstrated a MIC for voriconazole in the untreated group (4µg per ml), when compared to the group treated with cyp51A-specific siRNA and MDR1-specific siRNA, both at concentrations of 25 and 50nM, yielding 2µg per ml and 1µg per ml when 25 nM was applied and 2µg per ml and 0.5µg per ml when the concentration doubled to 50 nM. Conclusion: In this study, we suggested that siRNA-mediated specific inhibition of cyp51A and MDR1 genes play roles in voriconazole-resistant A.flavus strain and these could be apt target genes for inactivation. The current study promises a bright prospect for the treatment of invasive aspergillosis through the effective deployment of RNAi and gene therapy.

Background: Global reports have highlighted the increasing prevalence of Candida tropicalis infections as well as organism(') s drug resistance. This study aimed at identifying azole resistance markers in clinical isolates of C. tropicalis, which will be a great resource for developing new drugs., Methods: Two susceptible and resistant isolates of C. tropicalis were recovered from an epidemiological investigation of candidiasis in immunocompromised patients. C. tropicalis ATCC 750 was used as reference strain. Antifungal susceptibility to fluconazole and itraconazole was determined using Clinical and Laboratory Standards Institute (CLSI) method. Complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) technology and real-time reverse-transcriptase (RT) PCR were used for identification of potential genes involved in azole resistance of C. tropicalis clinical isolates., Results: Five genes encoding the following enzymes were identified as superoxide dismutase (SOD) implicated in antioxidant defense, ornithine aminotransferase (OAT), acetyl ornithine aminotransferase (ACOAT), adenosylmethionine-8-amino-7-oxononanoate aminotransferase (DAPA AT), and 4-aminobutyrate aminotransferase (ABAT)-belonging to pyridoxal phosphate (PLP) dependent enzymes and acting in an important physiological role in many fungal-cell cycles. Real-time RT-PCR confirmed mRNA level of the aforementioned genes., Conclusion: Our findings showed that factors such as PLP-dependent enzymes and SOD might be implicated in drug resistance in C. tropicalis clinical isolate. Therefore, further studies are required to explore the accurate biological functions of the mentioned genes that would be helpful for effective drug development., (© 2015 Wiley Periodicals, Inc.)

Background and Purpose: Fusarium species are avid producers of secondary toxic and carcinogenic metabolites such as fumonisin. Contamination of food and feed products with fumonisin can be hazardous to the health of humans and animals and may lead to agricultural loss. Accordingly, in this study, we aimed to evaluate the effects of Candida parapsilosis on the growth and fumonisin production of Fusarium species., Materials and Methods: Mycelial growth rate of 26 Fusarium isolates, including F. verticillioides (n=6), F. proliferatum (n=18), F. solani (n=1), and F. oxysporum (n=1), in the presence of 42 C. parapsilosis strains was investigated by pour-plate method. The decline in fumonisin production was measured in co-cultured fungi in coarsely ground maize after four weeks of incubation in the dark at 22°C, using ELISA technique. For data analysis, paired t-test was performed, using SPSS version 20., Results: The mycelial growth and fumonisin production of Fusarium isolates significantly decreased in the presence of C. parapsilosis in comparison with the control cultures (P<0.05). The percentage of mycelial growth inhibition ranged from 56.36% to 74.54%. The minimum and maximum decline in total fumonisin production was 12% and 78%, respectively. F. oxysporum and F. solani were found to be minor fumonisin producers among the studied Fusarium species. On the other hand, a decline was reported in the growth of Fusarium species and fumonisin production in the presence of C. parapsilosis ., Conclusion: C. parapsilosis showed notable inhibitory activities against Fusarium isolates. Therefore, this fungal species could be considered as a biocontrol agent against the growth and fumonisin production of toxigenic Fusarium species in the future., Competing Interests: None.

Background: Voriconazole Resistance (VRC-R) in Aspergillus flavus isolates impacts the management of aspergillosis, since azoles are the first choice for prophylaxis and therapy. However, to the best of our knowledge, the mechanisms underlying voriconazole resistance are poorly understood., Objectives: The present study was designed to evaluate mRNA expression levels of cyp51A and mdr1 genes in voriconazole resistant A. flavus by a Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique., Materials and Methods: Five A. flavus isolates with resistance to VRC were examined by a RT-PCR approach., Results: Four out of five isolates revealed cyp51A and mdr1 mRNA overexpression. Interestingly, the isolate, which was negative for cyp51A and mdr1 mRNA expression showed a high voriconazole Minimum Inhibitory Concentration (MIC). Furthermore, a computational-based analysis predicted that voriconazole resistance could be mediated through cooperation with a network protein interaction., Conclusions: Our experimental and in silico findings may provide new insight in the complex molecular pathways of drug resistance and also could assist design an efficient therapeutic strategy for aspergillosis treatment.

Background and Purpose: Tinea capitis and tinea unguium are regarded as global public health concerns. The purpose of the present study was to identify the etiological agents of tinea capitis and tinea unguium in patients, referring to the Central Laboratory of Yazd University of Medical Sciences, Yazd, Iran., Materials and Methods: This study was conducted during 2014-2015. Skin scraping, scalp hair, and nail clipping specimens were collected from 134 patients (80 males and 54 females) with clinical features suggesting fungal involvement. Direct microscopic examinations were carried out, using potassium hydroxide 10%, while culture studies were performed on Sabouraud dextrose agar, containing chloramphenicol and cycloheximide at 28 ° C for four weeks. Fungal colonies were identified based on their macroscopic and microscopic characteristics, as well as supplementary diagnostic tests., Results: Among 134 patients, 12 cases showed positive results on direct examination and culture studies. The frequency of infections was equal among male and female subjects. Among 12 affected cases, the frequency of tinea capitis and tinea unguium was 91.6% and 8.4%, respectively. Microsporum canis (50%) was the most prevalent species, followed by Trichophyton verrucosum (25%) and Trichophyton mentagrophytes (25%). Also, tinea unguium, caused by T. mentagrophytes, was found in a female patient., Conclusion: The etiological agents of scalp and nail dermatophytosis have changed in Yazd over the past 13 years. In the present study, replacement of anthropophilic dermatophytes by zoophilic species was noteworthy, highlighting the necessity of efficient surveillance for the management and prevention of infections., Competing Interests: There was no conflict of interest in the present study.

Background and Purpose: Dermatophytosis is one of the most common infections of skin, hair, and nails, caused by a group of keratinophilic fungi known as dermatophytes. Species identification of these fungi is of great significance from epidemiological and therapeutic points of view. The objective of the present study was to investigate dermatophytosis and its causative agents in patients, referring to the Central Mycology Laboratory of Yazd University of Medical Sciences, Yazd, Iran., Materials and Methods: In total, 139 clinically suspected cases of dermatophytosis were examined during 12 months from February 2014 to February 2015. Skin scrapings were assessed through direct microscopic examinations and culture studies. Dermatophyte isolates were identified based on colony morphology on potato dextrose agar and dermatophyte test medium, nutritional requirements, urease and hair perforation tests, and microscopic characteristics on slide cultures., Results: Dermatophytosis was mycologically confirmed in 26 (18.70%) out of 139 cases. Although there was a statistically insignificant difference between male and female subjects, men were dominantly affected. Infection was significantly common in the age group of ≤ 29 years (P<0.043). The most common clinical manifestation of dermatophytosis was tinea corporis (69.2%), followed by tinea cruris (15.4%), tinea manuum (11.5%), and tinea pedis (3.8%). Trichophyton mentagrophytes complex was the main etiologic agent (38.5%), followed by T. rubrum (23%), T. violaceum (15.5%), T. verrucosum (11.5%), Microsporum canis (7.7%), and Epidermophyton floccosum (3.8%)., Conclusion: In comparison with previous research, epidemiology of dermatophytosis has changed in Yazd over the past decades. Therefore, periodical investigations on the epidemiological aspects of this infection are required for efficient control and prevention of this cutaneous dermatophytic disease., Competing Interests: There was no conflict of interest in the present study.

Background: The production and development of an effective fungicidal drug requires the identification of an essential fungal protein as a drug target. Aconitase (ACO) is a mitochondrial protein that plays a vital role in tricarboxylic acid (TCA) cycle and thus production of energy within the cell., Objectives: The current study aimed to sequence Candida krusei ACO gene and determine any amino acid residue differences between human and fungal aconitases to obtain selective inhibition., Materials and Methods: Candida krusei (ATCC: 6258) aconitase gene was determined by 5'Rapid Amplification of cDNA Ends (RACE) method and degenerate Polymerase Chain Reaction (PCR) and analyzed using bioinformatics softwares., Results: One thousand-four hundred-nineteen nucleotide of C. krusei aconitase gene were clarified and submitted in Genbank as a partial sequence and then taxonomic location of C. krusei was determined by nucleotide and amino acid sequences of this gene. The comparison of nucleotide and amino acid sequences of Candida species ACO genes showed that C. krusei possessed characteristic sequences. No significant differences were observed between C. krusei and human aconitases within the active site amino acid residues., Conclusions: Results of the current study indicated that aconitase was not a suitable target to design new anti-fungal drugs that selectively block this enzyme.

Background: The aim of this study was to detect fungi in atherosclerotic plaques and investigate their possible role in atherosclerosis., Methods: Coronary atherosclerotic plaques specimen were obtained from patients with atherosclerosis. Direct examination, culture, histopathology study, PCR and sequencing were performed to detect/identify the mycotic elements in the plaques. Age, sex, smoking, obesity, hypertension, hyperlipidemia, family history of heart diseases and diabetes were considered and data were analyzed using Chi Square test by SPSS version 15., Results: A total of 41 specimens were analyzed. Direct examination for fungal elements was negative in all cases but in culture only one specimen grew as a mold colony. The presence of fungal elements were confirmed in 6 and 2 tissue sections stained by Gomori methenamine silver and Hematoxylin and Eosin methods, respectively. Using PCR, 11 cases were positive for fungi. The DNA sequence analysis of six positive specimens which were randomly selected revealed fungi as Candida albicans (n=3), Candida guilliermondii (n=2) and Monilia sp. (n=1)., Conclusion: A significant association between the presence of fungi in atherosclerotic plaques and severity of atherogenesis and atherosclerotic disease was not found. This could be due to limited numbers of patients included in our study. However, the presence of fungal elements in 26.8% of our specimens is considerable and the results does not exclude the correlation between the presence of fungi with atherosclerosis and coronary artery disease.

Background: Candida spp. is the most common organisms involved in fungal infections in the high risk patients. It causes the greatest number of invasive candidiasis. Fluconazole is effective in treating mucosal candidiasis. However, resistance to fluconazole and other azoles antifungal drugs is an important clinical problem to treat candidiasis. Caspofungin is more effective against Candida species such as some azoles-resistant isolates., Objectives: The current study aimed to investigate the susceptibilities of clinical fluconazole-resistant and fluconazole - susceptible dose- dependent Candida species to caspofungin., Materials and Methods: In the Minimum Inhibitory Concentration (MIC) test, 207 Candida species and other yeasts isolated from Iranian patients (each isolated from a high-risk patient) were evaluated. The yeasts were differentiated by standard mycological methods, CHROM agar Candida, and verified by API20C.AUX. In vitro susceptibilities were determined using Broth Micro Dilution (BMD) method described in the Clinical Laboratory Standards Institute M27-A3. MICs were noted after 24 and 48 hours of incubation., Results: The most frequently isolated species were Candida albicans (52.2%), C. glabrata (24.6%), followed by C. tropicalis (7.7%) and C. krusei (3.4%). MICs of caspofungin against 87% of C. albicans and 90% of C. glabrata and C. tropicalis isolates were 2 μg/mL and for C. krusei were 4 μg/mL, respectively. The results revealed that only 20 out of 207 isolates (9.7%) were non-sensitive to caspofungin. Caspofungin non-susceptible isolates were isolated from the patients with cancer, diabetes and AIDS; and not in the species isolated from patients with other underlying diseases., Conclusions: Caspofungin appears more effective in vitro against Iranian fluconazole-resistant Candida isolates and some other yeasts.

Background and Purpose: Candida species constitute an important group of opportunistic fungi, which cause various clinical diseases. Considering the resistance of some Candida species to conventional antifungal agents, treatment of such cases may be challenging and complicated. The purpose of this study was to evaluate and compare the antifungal activities of Euphorbia macroclada latex and fluconazole against different Candida species., Materials and Methods: A total of 150 Candida isolates including C. albicans (n=77), C. glabrata (n= 28), C. parapsilosis (n=23), C. tropicalis (n=15), C. krusei (n=4), C. famata (n=1), C. kefyr (n=1) and C. inconspicua (n=1) were included in this study. In vitro antifungal activities of Euphorbia macroclada latex and fluconazole against these Candida species were evaluated, according to M27-A2 protocol on broth macrodilution method by the Clinical and Laboratory Standards Institute (CLSI)., Results: Among 150 Candida isolates, 98 isolates (65.33%), i.e., C . albicans (n=41), C. glabrata (n=23), C. tropicalis (n=12) and C. parapsilosis (n=22) with minimal inhibitory concentration (MIC) ≤ 8 μg/ml were susceptible to fluconazole. Resistance to fluconazole was noted in 15 isolates, i.e., C. albicans (n=10), C. glabrata (n=2), C. krusei (n=1), C. kefyr (n=1), and C. inconspicua (n=1), with MICs of 64 µg/ml. The remaining isolates (n=37) including C. albicans (n=26), C. glabrata (n=3), C. tropicalis (n=3), C. parapsilosis (n=1), C. krusei (n=3) and C. famata (n=1) with MIC= 16-32 µg/ml showed dose-dependent susceptibility. The latex of Euphorbia macroclada was able to inhibit the growth of 30 out of 150 tested Candida isolates with MIC range of 128-512 µg/ml. These isolates were as follows: C. albicans (n=2), C. glabrata (n=4), C. parapsilosis (n=19), C. krusei (n=2) and C. tropicalis (n=3). Compared to other isolates, higher MIC values were noted for C. albicans and C. glabrata (512 µg/ml), respectively., Conclusion: The latex of Euphorbia macroclada showed notable antifungal activities against some pathogenic Candida species. Therefore, it can be potentially used as an alternative antifungal agent in future. However, further research is required to identify its active components., Competing Interests: None.

Background: Candida glabrata causes significant medical problems in immunocompromised patients. Many strains of this yeast are intrinsically resistant to azole antifungal agents, and treatment is problematic, leading to high morbidity and mortality rates in immunosuppressed individuals. The primary goal of this study was to investigate the genes involved in the drug resistance of clinical isolates of C. glabrata., Methods: The clinical isolates of C. glabrata were collected in an epidemiological survey of candidal infection in immunocompromised patients and consisted of four fluconazole and itraconazole resistant isolates, two fluconazole and itraconazole sensitive isolates, and C. glabrata CBS 138 as reference strain. Antifungal susceptibility patterns of the organisms were determined beforehand by the Clinical and Laboratory Standards Institute (CLSI). The potential gene(s) implicated in antifungal resistance were investigated using complementary DNA- Amplified Fragment Length Polymorphism (cDNA-AFLP). Semi-quantitative RT-PCR was carried out to evaluate the expression of gene(s) in resistant isolates as compared to sensitive and reference strains., Results and Conclusions: The aldo-keto-reductase superfamily (AKR gene) was upregulated in the resistant clinical isolates as assessed by cDNA-AFLP. Semi-quantitative RT-PCR revealed AKR mRNA expression approximately twice that seen in the sensitive isolates. Overexpression of the AKR gene was associated with increased fluconazole and itraconazole resistance in C. glabrata. The data suggest that upregulation of the AKR gene might give a new insight into the mechanism of azole resistance.

Presently appearance of resistance to antifungal agents among Aspergillus species is dramatically increasing. The objective of this study was to look at the in vitro activities of antifungal drugs against Iranian clinical (from nail, bronchoalveolar lavage, paranasal sinus) isolated A. flavus strains. The susceptibility of 45 aflatoxigenic and non-aflatoxigenic Aspergillus flavus strains were evaluated to six antifungal agents (caspofungin, itraconazole, amphotericin B, ketoconazole, fluconazole, nystatin) using CLSI M38-A2 broth microdilution method. The results indicated that 57.1%, 28.6% of aflatoxigenic and 25.8%, 6.5% of non-aflatoxigenic isolates were susceptible to caspofungin, amphotericin B respectively. All isolates but one aflatoxigenic strain were sensitive to ketoconazole. All 45 strains showed to be resistant to nystatin. Also 64.28%, 92.9% of aflatoxigenic and 64.51%, 100% of non-aflatoxigenic isolates were resistant to fluconazole and itraconazole in ranking order. There was no statistically significant difference between the susceptibilities of aflatoxigenic and non-aflatoxigenic strains of A. flavus to tested antifungal agents., (© 2012 Tehran University of Medical Sciences. All rights reserved.)

Background and the Purpose of the Study: Candida species are the agents of local and systemic opportunistic infections and have become a major cause of morbidity and mortality in the last few decades. Azole resistance in Candida krusei (C. krusei) species appears to be the result of gene alterations in relation to the ergosterol biosynthesis pathway, as well as efflux pumps. The main objective of this study was to examine the RNA expression of ERG11 in C. krusei which had been identified to be resistance to azoles., Methods: The ERG11 mRNA expression was investigated in four Iranian clinical isolates of C. krusei, which were resistant to fluconazole and itraconazole by a semiquantitative RT-PCR., Results: The mRNA expression levels were observed in all four isolates by this technique. Furthermore, it was found that ERG11 expression levels vary among four representative isolates of C. krusei. Although DNA sequencing revealed no significant genetic alteration in the ERG11 gene, one heterozygous polymorphism was observed in two isolates, but not in others. This polymorphism was found in the third base of codon 313 for Thr (ACT>ACC)., Major Conclusion: Even though such a polymorphism creates a new Ear1 restriction site, no significant effect was found on the resistance of C. krusei to azoles. RESULTS of this investigation are consistent with previous studies and may provide further evidence for the genetic heterogeneity and complexity of the ergosterol biosynthetic pathway or efflux pumps.