scholarly journals Mechanisms of azole resistance in 52 clinical isolates of Candida tropicalis in China

2012 ◽  
Vol 68 (4) ◽  
pp. 778-785 ◽  
Author(s):  
C. Jiang ◽  
D. Dong ◽  
B. Yu ◽  
G. Cai ◽  
X. Wang ◽  
...  
Keyword(s):  
Candida Tropicalis ◽  
Clinical Isolates ◽  
Azole Resistance

scholarly journals Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates

2016 ◽  
Vol 60 (6) ◽  
pp. 3653-3661 ◽  
Author(s):  
Min Ji Choi ◽  
Eun Jeong Won ◽  
Jong Hee Shin ◽  
Soo Hyun Kim ◽  
Wee-Gyo Lee ◽  
...  
Keyword(s):  
Amino Acid ◽  
Clinical Features ◽  
Candida Tropicalis ◽  
Resistance Mechanisms ◽  
Therapeutic Failure ◽  
Clinical Isolates ◽  
Azole Resistance ◽  
Amino Acid Substitutions ◽  
Content Type ◽  
Expression Levels

We investigated the azole resistance mechanisms and clinical features of fluconazole-nonsusceptible (FNS) isolates ofCandida tropicalisrecovered from Korean surveillance cultures in comparison with fluconazole-less-susceptible (FLS) isolates. Thirty-five clinical isolates ofC. tropicalis, comprising 9 FNS (fluconazole MIC, 4 to 64 μg/ml), 12 FLS (MIC, 1 to 2 μg/ml), and 14 control (MIC, 0.125 to 0.5 μg/ml) isolates, were assessed.CDR1,MDR1, andERG11expression was quantified, and theERG11andUPC2genes were sequenced. Clinical features of 16 patients with FNS or FLS bloodstream isolates were analyzed. Both FNS and FLS isolates had >10-fold higher mean expression levels ofCDR1,MDR1, andERG11genes than control isolates (Pvalues of <0.02 for all). When FNS and FLS isolates were compared, FNS isolates had 3.4-fold higher meanERG11expression levels than FLS isolates (P= 0.004), but there were no differences in those ofCDR1orMDR1. Of all 35 isolates, 4 (2 FNS and 2 FLS) and 28 (8 FNS, 11 FLS, and 9 control) isolates exhibited amino acid substitutions in Erg11p and Upc2p, respectively. Both FNS and FLS bloodstream isolates were associated with azole therapeutic failure (3/4 versus 4/7) or uncleared fungemia (4/6 versus 4/10), but FNS isolates were identified more frequently from patients with previous azole exposure (6/6 versus 3/10;P= 0.011) and immunosuppression (6/6 versus 3/10;P= 0.011). These results reveal that the majority of FNSC. tropicalisisolates show overexpression ofCDR1,MDR1, andERG11genes, and fungemia develops after azole exposure in patients with immunosuppression.

Pathogenicity of Candida tropicalis and Candida albicans after gastrointestinal inoculation in mice

1980 ◽  
Vol 29 (2) ◽  
pp. 808-813 ◽  
Author(s):  
J R Wingard ◽  
J D Dick ◽  
W G Merz ◽  
G R Sandford ◽  
R Saral ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mouse Model ◽  
Lung Tissue ◽  
Candida Tropicalis ◽  
Cytotoxic Drugs ◽  
Clinical Isolates ◽  
Yeast Cells ◽  
Gastrointestinal Mucosa ◽  
Compromised Host ◽  
Adult Mice

The ability of clinical isolates of Candida albicans and candida tropicalis to invade through normal and damaged gastrointestinal mucosa was determined. Adult mice were treated with either gentamicin or gentamicin and cytarabine. Suspensions of yeast cells (10(7)) were administered through a catheter intraesophageally. Invasion was determined by culturing liver, kidney, and lung tissue from mice sacrificed after 48 h. C. albicans and C. tropicalis were incapable of invading through normal gastrointestinal mucosa in mice treated only with gentamicin. Two isolates of C. tropicalis penetrated the damaged gastrointestinal mucosa in 69% (49 of 71) of mice treated with gentamicin and cytarabine. In contrast, three isolates of C. albicans penetrated he damaged gastrointestinal mucosa in only 23% (14 of 62) of mice. These results suggest that C. tropicalis is more capable of invading through damaged gastrointestinal mucosa than C. albicans. The observations in this mouse model parallel those seen in patients on cytotoxic drugs. Therefore, this model offers a tool for investigation of the pathogenicity of these organisms in a model analogous to the compromised host.

Azole resistance among clinical isolates of Aspergillus fumigatus in Lima-Peru

2019 ◽  
Vol 58 (1) ◽  
pp. 54-60 ◽  
Author(s):  
Beatriz Bustamante ◽  
Luis Ricardo Illescas ◽  
Andrés Posadas ◽  
Pablo E Campos
Keyword(s):  
Aspergillus Fumigatus ◽  
Latin American ◽  
Pcr Amplification ◽  
Sensu Stricto ◽  
Clinical Isolates ◽  
Azole Resistance ◽  
Molecular Testing ◽  
Naive Patient ◽  
In Vitro Susceptibility

Abstract Azole resistance among Aspergillus fumigatus isolates, which is mainly related to mutations in the cyp51A gene, is a concern because it is rising, worldwide disseminated, and associated with treatment failure and death. Data on azole resistance of aspergillus from Latin American countries is very scarce and do not exist for Peru. Two hundred and seven Aspergillus clinical isolates collected prospectively underwent mycology and molecular testing for specie identification, and 143 isolates were confirmed as A. fumigatus sensu stricto (AFSS). All AFSS were tested for in vitro azole susceptibility, and resistant isolates underwent PCR amplification and sequencing of the whole cyp51A gene and its promoter. The in vitro susceptibility showed a minimal inhibitory concentration (MIC) range, MIC50 and MIC90 of 0.125 to &gt;16, 0.25, and 0.5 μg/ml for itraconazole; 0.25 to 2, 0.5, and 0.5 μg/ml for voriconazole; and 0.003 to 1, 0.06, and 0.125 μg/ml for posaconazole. Three isolates (2%) showed resistance to itraconazole and exhibited different mutations of the cyp51A gene. One isolate harbored the mutation M220K, while a second one exhibited the G54 mutation plus a modification in the cyp51A gene promoter. The third isolate, from an azole naive patient, presented an integration of a 34-bp tandem repeat (TR34) in the promoter region of the gene and a substitution of leucine 98 by histidine (L98H). The three source patients had a diagnosis or suspicion of chronic pulmonary aspergillosis.

scholarly journals Molecular mechanisms of azole resistance in Candida tropicalis isolates causing invasive candidiasis in China

2019 ◽  
Vol 25 (7) ◽  
pp. 885-891 ◽  
Author(s):  
X. Fan ◽  
M. Xiao ◽  
D. Zhang ◽  
J.-J. Huang ◽  
H. Wang ◽  
...  
Keyword(s):  
Candida Tropicalis ◽  
Invasive Candidiasis ◽  
Molecular Mechanisms ◽  
Azole Resistance

scholarly journals Role of ATP-Binding-Cassette Transporter Genes in High-Frequency Acquisition of Resistance to Azole Antifungals in Candida glabrata

2001 ◽  
Vol 45 (4) ◽  
pp. 1174-1183 ◽  
Author(s):  
Dominique Sanglard ◽  
Francoise Ischer ◽  
Jacques Bille
Keyword(s):  
Abc Transporter ◽  
High Frequency ◽  
Candida Glabrata ◽  
Antifungal Agents ◽  
Clinical Isolates ◽  
Azole Resistance ◽  
Atp Binding ◽  
Transporter Gene ◽  
Atp Binding Cassette

ABSTRACT Candida glabrata has been often isolated from AIDS patients with oropharyngeal candidiasis treated with azole antifungal agents, especially fluconazole. We recently showed that the ATP-binding-cassette (ABC) transporter gene CgCDR1 was upregulated in C. glabrata clinical isolates resistant to azole antifungal agents (D. Sanglard, F. Ischer, D. Calabrese, P. A. Majcherczyk, and J. Bille, Antimicrob. Agents Chemother. 43:2753–2765, 1999). Deletion of CgCDR1 in C. glabrata rendered the null mutant hypersusceptible to azole derivatives and showed the importance of this gene in mediating azole resistance. We observed that wild-type C. glabrata exposed to fluconazole in a medium containing the drug at 50 μg/ml developed resistance to this agent and other azoles at a surprisingly high frequency (2 × 10−4 to 4 × 10−4). We show here that this high-frequency azole resistance (HFAR) acquired in vitro was due, at least in part, to the upregulation ofCgCDR1. The CgCDR1 deletion mutant DSY1041 could still develop HFAR but in a medium containing fluconazole at 5 μg/ml. In the HFAR strain derived from DSY1041, a distinct ABC transporter gene similar to CgCDR1, calledCgCDR2, was upregulated. This gene was slightly expressed in clinical isolates but was upregulated in strains with the HFAR phenotype. Deletion of both CgCDR1 and CgCDR2suppressed the development of HFAR in a medium containing fluconazole at 5 μg/ml, showing that both genes are important mediators of resistance to azole derivatives in C. glabrata. We also show here that the HFAR phenomenon was linked to the loss of mitochondria in C. glabrata. Mitochondrial loss could be obtained by treatment with ethidium bromide and resulted in acquisition of resistance to azole derivatives without previous exposure to these agents. Azole resistance obtained in vitro by HFAR or by agents stimulating mitochondrial loss was at least linked to the upregulation of both CgCDR1 and CgCDR2.

Effect of antifungals on itraconazole resistant Candida glabrata

2010 ◽  
Vol 5 (3) ◽  
pp. 318-323 ◽  
Author(s):  
Soňa Kucharíková ◽  
Patrick Dijck ◽  
Magdaléna Lisalová ◽  
Helena Bujdáková
Keyword(s):  
Amphotericin B ◽  
Biofilm Formation ◽  
Candida Glabrata ◽  
Antifungal Agents ◽  
Inhibitory Concentration ◽  
Clinical Isolates ◽  
Azole Resistance ◽  
Low Concentrations ◽  
Reduction Assay ◽  
Very High

AbstractIn the last decade, infections caused by Candida glabrata have become more serious, particularly due to its decreased susceptibility to azole derivatives and its ability to form biofilm. Here we studied the resistance profile of 42 C. glabrata clinical isolates to different azoles, amphotericin B and echinocandins. This work was also focused on the ability to form biofilm which plays a role in the development of antifungal resistance. The minimal inhibitory concentration testing to antifungal agents was performed according to the CLSI (Clinical and Laboratory Standards Institute) M27-A3 protocol. Quantification of biofilm was done by XTT reduction assay. All C. glabrata clinical isolates were resistant to itraconazole and sixteen also showed resistance to fluconazole. All isolates remained susceptible to voriconazole. Amphotericin B was efficient in a concentration range of 0.125–1 mg/L. The most effective antifungal agents were micafungin and caspofungin with the MIC100 values of ≤0.0313–0.125 mg/L. Low concentrations of these agents reduced biofilm formation as well. Our results show that resistance of different C. glabrata strains is azole specific and therefore a single azole resistance cannot be assumed to indicate general azole resistance. Echinocandins proved to have very high efficacy against clinical C. glabrata strains including those with ability to form biofilm.

scholarly journals Multiplecyp51A-Based Mechanisms Identified in Azole-Resistant Isolates of Aspergillus fumigatus from China

2015 ◽  
Vol 59 (7) ◽  
pp. 4321-4325 ◽  
Author(s):  
Musang Liu ◽  
Rong Zeng ◽  
Lili Zhang ◽  
Dongmei Li ◽  
Guixia Lv ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Clinical Isolates ◽  
Resistant Isolate ◽  
Azole Resistance ◽  
Content Type ◽  
Resistant Strains

ABSTRACTSeventy-twoA. fumigatusclinical isolates from China were investigated for azole resistance based on mutations ofcyp51A. We identified four azole-resistant strains, among which we found three strains highly resistant to itraconazole, two of which exhibit the TR34/L98H/S297T/F495I mutation, while one carries only the TR34/L98H mutation. To our knowledge, the latter has not been found previously in China. The fourth multiazole-resistant isolate (with only moderate itraconazole resistance) carries a new G432A mutation.

scholarly journals Identification of Azole Resistance Markers in Clinical Isolates ofCandida tropicalisUsing cDNA-AFLP Method

2015 ◽  
Vol 30 (3) ◽  
pp. 266-272 ◽  
Author(s):  
Ali Kanani ◽  
Farideh Zaini ◽  
Parivash Kordbacheh ◽  
Mehraban Falahati ◽  
Sassan Rezaie ◽  
...  
Keyword(s):  
Clinical Isolates ◽  
Azole Resistance ◽  
Resistance Markers

ERG11 mutations are associated with high-level azole resistance in clinical Candida tropicalis isolates, a Singapore study

Mycoscience ◽  
2017 ◽  
Vol 58 (2) ◽  
pp. 111-115 ◽  
Author(s):  
Ka Lip Chew ◽  
Janet W.S. Cheng ◽  
Roland Jureen ◽  
Raymond T.P. Lin ◽  
Jeanette W.P. Teo
Keyword(s):  
Candida Tropicalis ◽  
Azole Resistance ◽  
High Level
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