Multidrug Resistance in Fungi

Gulshan, Kailash; Moye‐Rowley, W. Scott

doi:10.1128/ec.00254-07

Cited by 165 publications

(176 citation statements)

References 129 publications

Supporting

Mentioning

173

Contrasting

Unclassified

Order By: Relevance

“…It occurs in organisms ranging from bacteria to humans [1][2][3]. A common mechanism underlying this resistance is an amplification of the level of membrane proteins which function as drug extrusion pumps, belonging either to the ATPbinding-cassette (ABC) or to the major facilitator super families.…”

Section: Introductionmentioning

confidence: 99%

Putative role for ABC multidrug exporters in yeast quorum sensing

et al. 2009

View full text Add to dashboard Cite

a b s t r a c tPleiotropic drug resistance (PDR) transporters play essential roles in cell resistance to various toxic compounds in various organisms including bacteria, mammals and yeasts. A large group of PDR transporters have been described in yeasts so far, including those that are controlled by transcription factor Pdr1p. Here, we show that besides their role in removing extracellularly added toxic compounds, the Pdr5p and Snq2p transporters play important physiological roles and significantly influence the developmental phases and physiology of yeast populations growing in a liquid culture. They appear to be involved in population quorum sensing, which consequently influences transcription factor Pdr1p level via feedback regulation.

show abstract

Section: Introductionmentioning

confidence: 99%

Putative role for ABC multidrug exporters in yeast quorum sensing

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Additionally, in a worldwide survey of medical centers, a resistance rate of 5.8 % was reported, with most resistant isolates reported from China (Bowyer & Denning, 2014). One of the major mechanisms involved in the azole resistance of A. fumigatus is the modification of sterol 14a-demethylation, which is a key enzyme in the ergosterol biosynthetic pathway, encoded by CYP51A and CYP51B genes (Chen et al, 2005;Gulshan & Moye-Rowley, 2007). In fact, mutations at codons TR 34 /L98H, G54, M220, G138C and G432C have been identified in azole-resistant A. fumigatus strains (Chen et al, 2005;Gulshan & Moye-Rowley, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…One of the major mechanisms involved in the azole resistance of A. fumigatus is the modification of sterol 14a-demethylation, which is a key enzyme in the ergosterol biosynthetic pathway, encoded by CYP51A and CYP51B genes (Chen et al, 2005;Gulshan & Moye-Rowley, 2007). In fact, mutations at codons TR 34 /L98H, G54, M220, G138C and G432C have been identified in azole-resistant A. fumigatus strains (Chen et al, 2005;Gulshan & Moye-Rowley, 2007). Over 90 % of azole-resistant A. fumigatus isolates harbour a leucine-to-histidine substitution at codon 98, along with a 34 bp tandem repeat in the CYP51A promoter region.…”

Section: Introductionmentioning

confidence: 99%

High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?

Nabili

Shokohi

Moazeni

et al. 2016

Journal of Medical Microbiology

View full text Add to dashboard Cite

Triazole antifungal agents are the mainstay of aspergillosis treatment. As highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. In the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of Iran were processed and screened in terms of azole resistance (4 and 1 mg l À1 of itraconazole and voriconazole, respectively), using selective plates. Overall, 150 A. fumigatus isolates (71 clinical and 79 environmental isolates) were detected. The isolates were confirmed by partial sequencing of the b-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents were performed, based on the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The CYP51A gene was sequenced in order to detect mutations. The MIC of itraconazole against 10 (6.6 %) strains, including clinical (n=3, 4.2 %) and environmental (n=7, 8.8 %) strains, was higher than the breakpoint and epidemiological cut-off value. Based on the findings, the prevalence of azole-resistant A. fumigatus in Iran has increased remarkablyfrom 3.3 % to 6.6 % in comparison with earlier epidemiological research. Among resistant isolates, TR 34 /L98H mutations in the CYP51A gene were the most prevalent (n=8, 80 %), whereas other point mutations (F46Y, G54W, Y121F, G138C, M172V, F219C, M220I, D255E, T289F, G432C and G448S mutations) were not detected. Although the number of patients affected by azole-resistant A. fumigatus isolates was limited, strict supervision of clinical azole-resistant A. fumigatus isolates and persistent environmental screening of azole resistance are vital to the development of approaches for the management of azole resistance in human pathogenic fungi.

show abstract

“…Though bacterial drug resistance has been studied over for the last few decades, such studies for pathogenic fungi have got recent interest [12]. Treatment with antifungal drugs often results in the appearance of resistant strains of fungi.…”

Section: Introductionmentioning

confidence: 99%

Systems Biology Study of Yeast Mitogen Activated Protein Kinase (MAPK) Cascade for Novel Drug Target Identification against Fungal Pathogens

Babar¹,

Islam²,

Rahman³

et al. 2013

IJBBB

View full text Add to dashboard Cite

Abstract-Novel drug target identification and drug discovery are potential fields of systems biology which is recently being implemented against various pathogens based on differential biological processes of host and pathogen. Due to closer extent of biological similarity of eukaryotic fungal pathogens with their hosts, it has been urgent to find out novel drug targets against fungal pathogens. It is seen that mitogen activated protein kinase (MAPK) cascade transmits signals from outer cell surface to the nucleus and is involved in fungal survival mechanisms against environmental stress conditions. MAPK cascade molecules can be good targets of antifungal drugs to avoid fungal survival against conventional drugs. From these perspectives, systems biology approaches have been undertaken with an aim to assess the MAPK molecules as antifungal drug targets to find out the best one using Yeast (Saccharomyces cerevisiae) as model organism, Human as host and Candida albicans as pathogen. Comparative proteomic study, protein-protein interaction study, sequence and structural analysis study, molecular docking study and mathematical modeling study have been conducted in this regard. A combined prioritizing scoring system has been used to identify the most optimal MAPK target based on weighted decision matrix and combined matrix position score (CMPS), stability of the matrix position score (SD) and total score (TS) have been introduced. MAPKs having TS less than the average TS (72.55) were screened out as better MAPK targets. The approach predicts SLT2/MPK1 among the 11 MAPK molecules the best target of antifungal drugs having the low est TS (54.49).Index Terms-Antifungal drug, MAPK cascade, novel drug target, signal transduction pathway, systems biology.

show abstract

Multidrug Resistance in Fungi

Cited by 165 publications

References 129 publications

Putative role for ABC multidrug exporters in yeast quorum sensing

Putative role for ABC multidrug exporters in yeast quorum sensing

High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?

Systems Biology Study of Yeast Mitogen Activated Protein Kinase (MAPK) Cascade for Novel Drug Target Identification against Fungal Pathogens

Contact Info

Product

Resources

About