Research progress on drug resistance mechanism of Candida glabrata / 药学实践杂志

With the increasing proportion of Candida glabrata in patients with candidiasis, C. glabrata has become one of the most common pathogenic Candida in clinical practice. There are limited types of antifungal drugs, and the consequent problem of drug resistance is severely increasing, which brings difficulties to clinical treatment. The resistance mechanisms of C. glabrata to azoles, echinocandins and polyenes were reviewed in this paper.

Research progress on drug combination therapy against Candida albicans / 药学实践杂志

Candida albicans is one of the most common species of Candida, which is an important cause of invasive candidiasis in clinic. Due to the frequently use of classical antifungal agents, there are amounts of drug resistant C. albicans being isolated, causing the significantly decreasing of the efficacy of some antifungal agents in clinical treatment. Besides, the use of some compounds in clinic has been limited because of their toxicities. In such a context, drug combination therapy shows great potential on antifungal because of the synergy of different drugs or therapeutic methods that could bring, which could improve the weaknesses of single drug.

Comparison of the effect of miconazole and clotrimazole in the treatment of vulvovaginal candidiasis among women seen in a tertiary medical center from 2016 to 2020 / Philippine Journal of Obstetrics and Gynecology

Background@#Vulvovaginal Candidiasis (VVC) is one of the frequent infections of the female genital tract and is the second most common cause of vaginal infections after bacterial vaginosis. According to the Centers for Disease Control and Prevention, azoles are the first‑line treatment for VVC. Among the azoles available in the Philippines, only miconazole and clotrimazole are recommended for both pregnant and non‑pregnant women.@*Objective@#Compare the effect of miconazole versus clotrimazole in the treatment of vulvovaginal candidiasis among patients seen at the out‑patient department in a tertiary hospital@*Materials and Methods@#This involved review of the records of patients diagnosed with VVC in a tertiary medical center from 2016 to 2020. All records of women, pregnant and non‑pregnant, wherein single‑dose 1200 mg miconazole or 6‑day 100 mg clotrimazole given vaginally were included@*Results@#Eleven out of the 316 records (3.46%) remained symptomatic after treatment, about 18.1% (2/161) from those who used miconazole and 81.8% (9/155) from those treated with clotrimazole (p 0.027). In terms of failure rate, for miconazole it was 1.2% (2/161), whereas for clotrimazole it was 5.8% (9/155). None of the charts were found to have recorded adverse reaction to the given treatment@*Conclusion@#Single‑dose miconazole intravaginal regimen has a higher clinical cure rate than the 6‑day clotrimazole intravaginal treatment. Thereby, single‑dose intravaginal miconazole has the potential to improve patient compliance and treatment outcome at a lower cost

Azole Resistance and Detection of the ERG11 Gene in Clinical Candida albicans Isolated from Pregnant Women with Vulvovaginitis Attending Federal Medical Centre, Yenagoa, Nigeria

Introduction:Candida albicansis one of the most important aetiological agents causing vaginal candidiasis in pregnant women.Most women will experience at least one episode during their reproductive years. Antifungal resistance is a particular problem with Candida infections. Some types of Candida are increasingly resistant to the first-line and second-line antifungal medications.Objective:To investigate the azole susceptibility of Candida albicans(C. albicans) from pregnant vulvovaginal candidiasis patients and to detect ERG11gene in these azole resistance isolates.Methods:Forty-one clinical isolates of C. albicanswere collected. Azole susceptibility was tested in vitrousing microdilution techniques.The ERG11genes of 27 isolates of C. albicans(All resistant to azoles) were amplified using PCR method

Detection of Azole Drug Resistance of the Aspergillus Species Cyp51a Gene by PCR

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity pulmonary disease occurring in individuals with asthma or cystic fibrosis. In these patients, it is characterized by transient pulmonary infiltrates, reversible airway obstruction, eosinophilia

Systematic review and meta-analysis on oral azoles for the treatment of pityriasis versicolor

@#<p style="text-align: justify;"><strong>Background:</strong> Oral azole drugs are a second-line option for the treatment of pityriasis versicolor but evidence on their efficacy and safety is unclear. Objectives. To determine the efficacy and safety of oral azoles in the treatment of patients with pityriasis Versicolor.</p><p style="text-align: justify;"><strong>Methods</strong>: We searched MEDLINE, CENTRAL, EMBASE, LILACS, and HERDIN, from inception to the period between January to February 2014. We did not restrict the search by language or publication status. We included randomized controlled trials (RCTs) that compared the efficacy of oral azoles with placebo or no treatment, with topical agents, other oral azoles or dosing regimens in the treatment of pityriasis Versicolor, and that measured any of the pre-specified outcomes (mycologic cure, clinical cure, recurrence, duration to cure, time-to-cure, and quality of life). For adverse effects, we also included non-randomized studies (NRS). We used Cochrane methods to select studies, extract data, assess the risk of bias, pool studies, and calculate for treatment effects.</p><p style="text-align: justify;"><strong>Results:</strong> We included 38 RCTs (n=2894) and 56 NRS (n=3452). Overall, there were few pooled studies and evidence was low to moderate quality. Oral azoles were more effective than placebo (mycologic cure, RR 11.34, 95% CI 4.90, 26.28; 3 RCTs, n=131; I2=0%; low quality of evidence) and as effective as topical agents (mycologic cure, RR 1.02, 95% CI 0.86, 1.21; 4 RCTs, n=232; I2=60%; moderate quality of evidence).There were few adverse effects and were mostly minor and transient.</p><p style="text-align: justify;"><strong>Conclusions:</strong> Oral azoles may be more effective than placebo, and are probably as effective as topical agents in the treatment of PV. Triazoles are probably as effective as ketoconazole. Adverse effects were few, mostly minor, and transient.</p>

Cis-2-dodecenoic Acid Mediates Its Synergistic Effect with Triazoles by Interfering with Efflux Pumps in Fluconazole-resistant Candida albicans / 生物医学与环境科学（英文）

OBJECTIVE@#To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo.@*METHODS@#Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR).@*RESULTS@#BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 μg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis.@*CONCLUSION@#The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.

Two natural molecules preferentially inhibit azole-resistant Candida albicans with MDR1 hyperactivation / 中国天然药物

Antifungal drug resistance is a significant clinical problem, and antifungal agents that can evade resistance are urgently needed. In infective niches, resistant organisms often co-existed with sensitive ones, or a subpopulation of antibiotic-susceptible organisms may evolve into resistant ones during antibiotic treatment and eventually dominate the whole population. In this study, we established a co-culture assay in which an azole-resistant Candida albicans strain was mixed with a susceptible strain labeled with green fluorescent protein to mimic in vivo conditions and screen for antifungal drugs. Fluconazole was used as a positive control to verify the validity of this co-culture assay. Five natural molecules exhibited antifungal activity against both susceptible and resistant C. albicans. Two of these compounds, retigeric acid B (RAB) and riccardin D (RD), preferentially inhibited C. albicans strains in which the efflux pump MDR1 was activated. This selectivity was attributed to greater intracellular accumulation of the drugs in the resistant strains. Changes in sterol and lipid compositions were observed in the resistant strains compared to the susceptible strain, and might increase cell permeability to RAB and RD. In addition, RAB and RD interfered with the sterol pathway, further aggregating the decrease in ergosterol in the sterol synthesis pathway in the MDR1-activated strains. Our findings here provide an alternative for combating resistant pathogenic fungi.

Mucosal leishmaniasis: the experience of a Brazilian referral center

Abstract INTRODUCTION Pentavalent antimonials (Sbv) are the most commonly used drugs for the treatment of mucosal leishmaniasis (ML), despite their high toxicity and only moderate efficacy. The aim of this study was to report therapeutic responses with different available options for ML. METHODS This study was based on a review of clinical records of 35 patients (24 men and 11 women) treated between 2009 and 2015. RESULTS The median age of patients was 63 years, and the median duration of the disease was 24 months. Seventeen patients received Sbv, while nine patients were treated with liposomal amphotericin B (AmB), and another nine patients were treated with fluconazole. Patients treated with AmB received a total median accumulated dose of 2550mg. The mean duration of azole use was 120 days, and the daily dose ranged from 450 to 900mg. At the three-month follow-up visit, the cure rate was 35%, 67%, and 22% for Sbv, AmB, and azole groups, respectively. At the six-month follow-up visit, the cure rates for Sbv, AmB, and azole groups were 71%, 78%, and 33%, respectively. CONCLUSIONS There is a scarcity of effective ML treatment alternatives, and based on our observations, fluconazole is not a valid treatment option.

Azole Resistance Caused by Increased Drug Efflux in Candida glabrata Isolated from the Urinary Tract of a Dog with Diabetes Mellitus

A yeast-like organism was isolated from a urine sample of a 6-year-old neutered male miniature poodle dog with urinary tract infection, diabetes ketoacidosis, and acute pancreatitis. We identified the yeast-like organism to be Candida glabrata and found that this fungus was highly resistant to azole antifungal drugs. To understand the mechanism of azole resistance in this isolate, the sequences and expression levels of the genes involved in drug resistance were analyzed. The results of our analysis showed that increased drug efflux, mediated by overexpression of ATP transporter genes CDR1 and PDH1, is the main cause of azole resistance of the C. glabrata isolated here.

Synthesis and antifungal activity of the novel azole compounds / 药学实践杂志

Objective To design and synthesize novel triazole antifungal derivatives with 1 ,3 ,4-oxadiazole side chain for the study of antifungal activities. Methods Fourteen title compounds were synthesized via acylation ,aminolysis reaction ,cy-clization ,nucleophilic substitution ,etc. All the compounds were characterized by 1 H NMR ,MS spectra. The in vitro antifun-gal activities were evaluated against six human pathogenic fungi through the micro-broth dilution method. Results The title compounds exhibited strong antifungal activities against all the tested fungi ,especially against Candida albicans. Compounds 10d ,10i , 10l , and 10n were found to be the most effective , with a minimum inhibitory concentration (MIC80 ) of 0.003 9 μg/ml .They are 16-fold more potent than ICZ ( MIC80 0.062 5 μg/ml) and 64-fold more potent than FCZ (MIC80 0.25 μg/ml) .Conclusion The 1 ,3 ,4-oxadiazole side chain could affect the antifungal activities. That could be due to the prop-er incorporation between the 1 ,3 ,4-oxadiazole substituted phenyl ring with the target enzyme.

Study on the application of zoledronic acid in the treatment of osteoporotic vertebral compression fractures with PKP / 中国生化药物杂志

Objective To investigate the application effect of zoledronic acid on PKP after osteoporotic vertebral compression fractures. Methods According to different treatment methods, 80 cases of patients from January 2015 to January 2017 in Xi'an City, Hong hui Red Cross hospital diagnosis and treatment of osteoporotic vertebral compression fractures parallel PKP were divided into two groups. The patients in the control group were not treated with zoledronic acid, and the patients in the observation group were treated with zoledronic acid.The treatment effect and adverse reaction rate were compared between two groups. Results The treatment effect of the observation group was better than that of the control group, and the improvement of the clinical symptoms of the observation group was better than that of the control group, and the incidence of adverse reactions was lower than that of the control group, the difference was statistically significant (P<0.05). Conclusion The effect of zoledronic acid treatment on osteoporotic vertebral compression fractures after PKP is remarkable, which can effectively improve the patients' clinical symptoms, less adverse reactions, is widely used in clinical osteoporotic vertebral compression fractures after PKP holds.

Mechanism of azole resistance in the Candida albicans strains isolated from vulvovaginal candidiasis / 中国感染与化疗杂志

Objective To investigate the resistance rates of the Candida albicans strains isolated from patients with vulvovaginal candidiasis to 5 antifungal agents and examine the mechanism of azole resistance in these strains.Methods A total of 1 646 C.albicans strains were collected in Obstetrics and Gynecology Hospital of Fudan University from January to December 2015.The resistance rates of these isolates to five antifungal agents were analyzed.Azole-resistant (n=30),dose dependent sensitive (S-DD) (n=13),and susceptible isolates (n=10) were randomly selected from the microbiology laboratories of three obstetrics and gynecology hospitals in Shanghai.The expression levels of drug efflux pump related gene CDR1,CDR2,MDR1 and drug target enzyme gene ERG11 were analyzed by real-time fluorescence quantitative polymerase chain reaction (PCR).At the same time,the ERG11 and ERG3 genes were amplified by PCR and sequenced,and analyzed for resistance-related mutations.Results Of the 1 646 C.albicans strains,5.2％,3.2％,2.5％ and 2.1％ were resistant to itraconazole,voriconazole,fluconazole and 5-fluorocytosine,respectively.All isolates were sensitive to amphotericin B.The expression of ERG11 gene was significantly higher in S-DD group and azole-resistant group than in azole-sensitive group (P＜0.05).The expression of CDR1,CDR2 and MDR1 did not show significant difference among the three groups.There were 13 missense mutations in the ERG11 gene,of which T123I,P98S and Y286D amino acid substitutions were newly discovered.Both T123I and Y132H were identified in 26 resistant isolates,of which 16 gene mutation was detected in two pan-azole-resistant isolates.Conclusions The C.albicans strains isolated from vulvovaginal candidiasis showed higher resistance rates to azole antifumgal agents than that to 5-fluorocytosine and amphotericin B.Mutation and over-expression ofERG11 gene may be one of the prevalent molecular mechanisms underlying azole resistance in C.albicans.were pan-azole-resistant.In addition,the ERG3 heterozygous

Clinical efficacy of anti-helicobacter pylori in treatment of type 2 diabetes mellitus with helicobacter pylori infection / 中国综合临床

Objective To explore the clinical efficacy of anti-helicobacter pylori (HP) treatment on patients with type 2 diabetes mellitus and HP infection.Methods A total of 112 type 2 Diabetes patients were diagnosed with HP infection in Combine Traditional Chinese and Western Medicine Hospital of Taizhou from April 2012 to June 2016.These patients were divided into control and treatment group based on the preprandial blood glucose averages from lower to higher hierarchy.Thus,there were 56 patients in each of the two groups.The control group was given Motilium and Talcid for gastric symptoms in addition to anti-diabetes treatment,while the treatment was administered the same treatments as well as the quadruple anti-HP therapy (omeprazole,amoxicillin,clarithromycin and colloidal-bismuth-subcitrate,with Talcid stopped while colloidal-bismuth-subcitrate was administered).The anti-HP lasted for 14 days.The two groups were compared the gastric symptoms,the blood glucose levels,and the HbA1c one month after treatment.Half a year and one year post treatment,the two groups were compared the gastric mucus signs under gastroscopy.Results The improvement rates after treatment with the treatment group in abdominal pain,bloating,regurgitation,belching and diarrhea/constipation were 88.5％ (23/26),83.3％ (25/30),74.1％ (20/27),83.9％ (26/31),82.6％ (19/23),respectively,and with the control group being 29.2％(7/24),32.1％(9/28),28％(7/25),30.3％(10/33),18.2％ (4/22),respectively.The differences between the two groups were significant (x2=8.06,6.62,3.92,7.65,6.66,P＜0.05 or P＜0.01).The control group did not show significant changes in preprandial glucose levels,the glucose levels two hours post meals and the HbA1c(P＞0.05) while the treatment group showed statistically significant changes(P＜0.05 or P＜0.01).The differences in the three indicators after treatment between the two groups were significant (t =4.07,7.85,4.16,P＜ 0.05).The Gastric mucus signs under gastroscopy showed improvements in both groups after treatment.The improvement rates with the treatment group were 86.2％(25/29),86.7％ (13/15),77.8％ (14/18),72.7％ (8/11) respectively,with the control group being 36％ (9/16),27.3％ (3/11),13.3％ (2/15),14.3％ (1/7),respectively.The differences between the two groups were significant (x2 =6.71,4.12,4.38,3.85,P ＜ 0.05 or P＜ 0.01).The effectiveness rate,which was based on combined improvements in gastric symptoms,glucose levels and gastric mucus signs,was 76.8％ with the treatment group and 32.1％ with the control group.The difference was statistically significant (x2 =6.78,P＜0.01).Conclusion Anti-HP treatment can relieve the gastric symptoms,stabilize the glucose levels,and help to reverse the changed gastric mucus.All these can reduce the complications of the diabetes and improve the prognosis of the patients.

Progress of research on azole resistance in Aspergillus fumigatus / 中华流行病学杂志

Being an important clinical fungal pathogen,Aspergillus (A.)fumigatus can cause fatal invasive fungal infections.Azoles are the first line drugs in treating various Aspergillus-caused diseases.Worldwidely,reports related to azole resistance in A.fumigatus have been increasing which posing a threat on the effectiveness of clinically used azole and agricultural fungicides.Currently,it has become an important public health issue.In this review,we summarize findings from literature regarding the following areas:the occurrence of azole resistance in A.fumigatus,the molecular mechanisms of resistance,contributing factors for the emergence of azole resistance,evolution of resistant strains and related control and prevention measures.

Progress of research on azole resistance in Aspergillus fumigatus / 中华流行病学杂志

Being an important clinical fungal pathogen,Aspergillus (A.)fumigatus can cause fatal invasive fungal infections.Azoles are the first line drugs in treating various Aspergillus-caused diseases.Worldwidely,reports related to azole resistance in A.fumigatus have been increasing which posing a threat on the effectiveness of clinically used azole and agricultural fungicides.Currently,it has become an important public health issue.In this review,we summarize findings from literature regarding the following areas:the occurrence of azole resistance in A.fumigatus,the molecular mechanisms of resistance,contributing factors for the emergence of azole resistance,evolution of resistant strains and related control and prevention measures.

Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole-susceptible and fluconazole-resistant Candida glabrata isolates

In vitro interaction between tacrolimus (FK506) and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole) against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%), followed by that of the combination with ketoconazole (37%), against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata, a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%), itraconazole (73%), voriconazole (63%) and fluconazole (60%). The synergisms that we observed in vitro, notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.

Research the Expression of MDR1 Genes in Vaginal Candida Albicans Resistance to Azole Agents / 现代检验医学杂志

Objective To investigate the expression levels of MDR1 gene from azole resistant strains in vaginal Candidaalbi-cans.Methods 60 strains of Candida albicans from recurrent vagintis patients were collected and identified by CHROM agar from Aug.2011 to Aug.2012.The drug resistance was detected by disk diffusion method.According to the result of drug sensitivity test,the strains were diveded into four groups:sensitive group moderately susceptible or resistant to flucon-azole group moderately susceptible or resistant to detoconazole group and moderately susceptible or resistant to miconazole group.Each group was selected 12 strains randomly.The expression of the MDR1 gene in these 48 strains were detected by real-time RT-PCR and analysed the datas by t test statistics.Results There were 22 sensitive strains,26 strains of moder-ately susceptible or resistant to detoconazole,12 strains of moderately susceptible or resistant to fluconazole and 38 strains of moderately susceptible or resistant to miconazole in 60 strains of Candidaalbicans.The relative expression of MDR1 gene in sensitive group was 0.41±0.47,in moderately susceptible or resistant to detoconazole group fluconazole group and micon-azole group were 3.32±4.46,2.27±3.05 and 0.9±0.81 respectively.Compared with the sensitive group,t values of mod-erately susceptible or resistant to detoconazole group,fluconazole group and miconazole group were-2.177,-2.130 and-2.094.The expression level of MDR1 gene had no statistical significance between the sensitive strains and moderately sus-ceptible or resistant strains(P>0.05).Conclution The relationship between MDR1 expression and the resistance to azole agents in vaginal Candida albicans requires further study.

Caracterización de los mecanismos de resistencia a azoles en aislados clínicos chilenos de Candida albicans / Characterization of azole resistance mechanisms in Chilean clinical isolates of Candida albicans

Introduction: The commensal yeast Candida albicans, can cause superficial or systemic candidiasis in susceptible hosts. In Chile, azole antifungals are the most widely used drugs in the treatment of candidiasis. In a previous study performed at our center, 2.1 and 1.6% of clinical isolates of C. albicans were found to be resistant to fluconazole and voriconazole, respectively. Objective: To characterize the resistance mechanisms involved in azoles resistance in Chilean clinical isolates. Methodology: Eight resistant, nine susceptible-dose dependent (SDD) and 10 susceptible strains (n: 27) were selected according to the Clinical Laboratory Standards Institute (CLSI) M27-S3 criteria, from vaginal and urine samples. Mutations in the 408-488 region of the ERG11 gene were studied by sequencing, and the relative expression of ERG11 gene and efflux pump genes CDR1, CDR2 and MDR1, was evaluated by quantitative real-time PCR (q-PCR). Results: No mutations were detected in the ERG11 gene and its overexpression was found only in 12.5% of the resistant strains (1/8). The most prevalent mechanism of resistance was the over-expression of efflux pumps (62.5%; 5/8). Conclusion: The study of the expression of efflux pumps by q-PCR could be a useful diagnostic tool for early detection of azole resistance in C. albicans.

Introducción: Candida albicans es una levadura comensal capaz de causar una infección oportunista en hospederos susceptibles denominada candidiasis, que puede ser superficial o sistémica. En Chile, los antifúngicos más utilizados para el tratamiento de las candidiasis son los azoles. En un estudio previo en nuestro centro, se detectó que 2,1 y 1,6% de cepas clínicas de C. albicans fueron resistentes a fluconazol y voriconazol, respectivamente. Objetivo: Caracterizar los mecanismos de resistencia involucrados en la resistencia a azoles en cepas clínicas chilenas. Metodología: Según los criterios del Clinical Laboratory Standards Institute (CLSI) M27-S3, se seleccionaron ocho cepas resistentes, nueve cepas susceptibles dosis dependiente (SDD) y 10 cepas sensibles (n: 27), aisladas de flujo vaginal y orina. Se evaluó la presencia de mutaciones en la región 408-488 del gen ERG11 por secuenciación y la expresión relativa del gen ERG11 y de los genes de bombas de eflujo CDR1, CDR2 y MDR1 por RPC en tiempo real cuantitativa (q-PCR). Resultados: No se encontraron mutaciones en el gen ERG11 y la sobre-expresión de éste sólo se presentó en 12,5% de las cepas resistentes (1/8). El mecanismo prevalente en la cepas resistentes fue la sobre-expresión de bombas de eflujo encontrándose en 62,5% de las cepas resistentes (5/8). Conclusión: El estudio de la expresión bombas de eflujo por q-PCR podría ser una herramienta diagnóstica útil para la detección temprana de resistencia a azoles en C. albicans.

Mutation of P927S in PRD1 gene mediates azole resistance in Candida glabrata / 中华传染病杂志

Objective To investigate the role of PDR1 gene in azole-resistant Candida glabrata (C.glabrata).Methods Thirty-eight clinical isolates of C.glabrata were collected from five different hospitals.The minimal inhibitory concentrations (MIC) of azole antifungals including fluconazole,itraconazole and voriconazole against C.glabrata were determined by broth microdilution.Sequencing and amplification of PDR1 gene was achieved by real-time quantitative polymerase chain reaction (PCR).The mutation was cloned into an expression plasmid and then transferred into C.glabrata.The efflux of rhodamine 6G and drug sensitivity test were performed,and expressions of CDR1 and CDR2 were examined to verify function of mutation.Results Among these 38 isolates of C.glabrata,17 were resistant to at least one of azole antifungals.Moreover,mutations of PDR1 gene existed in every resistant isolates.Results of phenotyping test showed that in the isolate that expressed PDR1P927S,the expression of CDR1 and CDR2 were increased by 20.53 and 4.03 fold,respectively.And the fluorescence intensity of rhodamine 6G was decreased to 0.62 in efflux experiment.Conclusion P927S mutation of PDR1 gene could induce azole resistance of C.glabrata by increasing the expressions of CDR1 and CDR2,which results in drug resistance due to enhanced effect of efflux pump.