scholarly journals Recreation of in-host acquired single nucleotide polymorphisms by CRISPR-Cas9 reveals an uncharacterised gene playing a role in Aspergillus fumigatus azole resistance via a non-cyp51A mediated resistance mechanism

2019 ◽  
Vol 130 ◽  
pp. 98-106 ◽  
Author(s):  
Eloise Ballard ◽  
Jakob Weber ◽  
Willem J.G. Melchers ◽  
Seshu Tammireddy ◽  
Phillip D. Whitfield ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Aspergillus Fumigatus ◽  
Resistance Mechanism ◽  
Azole Resistance ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Quantitative Analysis of Single-Nucleotide Polymorphism for Rapid Detection of TR34/L98H- and TR46/Y121F/T289A-Positive Aspergillus fumigatus Isolates Obtained from Patients in Iran from 2010 to 2014

2015 ◽  
Vol 60 (1) ◽  
pp. 387-392 ◽  
Author(s):  
Faezeh Mohammadi ◽  
Seyed Jamal Hashemi ◽  
Jan Zoll ◽  
Willem J. G. Melchers ◽  
Haleh Rafati ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Quantitative Analysis ◽  
Single Nucleotide Polymorphisms ◽  
Aspergillus Fumigatus ◽  
Tandem Repeat ◽  
Promoter Region ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Content Type

ABSTRACTWe employed an endpoint genotyping method to update the prevalence rate of positivity for the TR34/L98H mutation (a 34-bp tandem repeat mutation in the promoter region of thecyp51Agene in combination with a substitution at codon L98) and the TR46/Y121F/T289A mutation (a 46-bp tandem repeat mutation in the promoter region of thecyp51Agene in combination with substitutions at codons Y121 and T289) among clinicalAspergillus fumigatusisolates obtained from different regions of Iran over a recent 5-year period (2010 to 2014). The antifungal activities of itraconazole, voriconazole, and posaconazole against 172 clinicalA. fumigatusisolates were investigated using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. For the isolates with an azole resistance phenotype, thecyp51Agene and its promoter were amplified and sequenced. In addition, using a LightCycler 480 real-time PCR system, a novel endpoint genotyping analysis method targeting single-nucleotide polymorphisms was evaluated to detect the L98H and Y121F mutations in thecyp51Agene of all isolates. Of the 172A. fumigatusisolates tested, the MIC values of itraconazole (≥16 mg/liter) and voriconazole (>4 mg/liter) were high for 6 (3.5%). Quantitative analysis of single-nucleotide polymorphisms showed the TR34/L98H mutation in thecyp51Agenes of six isolates. No isolates harboring the TR46/Y121F/T289A mutation were detected. DNA sequencing of thecyp51Agene confirmed the results of the novel endpoint genotyping method. By microsatellite typing, all of the azole-resistant isolates had genotypes different from those previously recovered from Iran and from the Dutch TR34/L98H controls. In conclusion, there was not a significant increase in the prevalence of azole-resistantA. fumigatusisolates harboring the TR34/L98H resistance mechanism among isolates recovered over a recent 5-year period (2010 to 2014) in Iran. A quantitative assay detecting a single-nucleotide polymorphism in thecyp51Agene ofA. fumigatusis a reliable tool for the rapid screening and monitoring of TR34/L98H- and TR46/Y121F/T289A-positive isolates and can easily be incorporated into clinical mycology algorithms.

Albendazole resistance induced in Ancylostoma ceylanicum is not due to single-nucleotide polymorphisms (SNPs) at codons 167, 198, or 200 of the beta-tubulin gene, indicating another resistance mechanism

2019 ◽  
Vol 118 (3) ◽  
pp. 837-849 ◽  
Author(s):  
Luis Fernando Viana Furtado ◽  
Pedro Henrique Nascimento de Aguiar ◽  
Luciana Werneck Zuccherato ◽  
Talita Tatiana Guimarães Teixeira ◽  
William Pereira Alves ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Resistance Mechanism ◽  
Nucleotide Polymorphisms ◽  
Ancylostoma Ceylanicum ◽  
Tubulin Gene ◽  
Beta Tubulin ◽  
Single Nucleotide ◽  
Beta Tubulin Gene

scholarly journals Interrogation of Related Clinical Pan-Azole-Resistant Aspergillus fumigatus Strains: G138C, Y431C, and G434C Single Nucleotide Polymorphisms incyp51A, Upregulation ofcyp51A, and Integration and Activation of TransposonAtf1in thecyp51APromoter

2011 ◽  
Vol 55 (11) ◽  
pp. 5113-5121 ◽  
Author(s):  
Ahmed M. Albarrag ◽  
Michael J. Anderson ◽  
Susan J. Howard ◽  
Geoff D. Robson ◽  
Peter A. Warn ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Resistance Mechanisms ◽  
Start Codon ◽  
Azole Resistance ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Content Type ◽  
Transcription Start Sites ◽  
Chronic Pulmonary Aspergillosis

ABSTRACTMultipleAspergillus fumigatusisolates from a patient with two aspergillomas complicating chronic pulmonary aspergillosis were pan-azole resistant. Microsatellite typing was identical for all isolates despite major phenotypic and some growth rate differences. Three differentcyp51Amutations were found (G138C, Y431C, and G434C), of which the first two were demonstrated by heterologous expression in a hypersusceptibleSaccharomyces cerevisiaestrain to be at least partly responsible for elevated MICs.cyp51Aandcyp51Bgene duplication was excluded, but increased expression ofcyp51Awas demonstrated in three isolates selected for additional study (7-to 13-fold increases). In the isolate with the greatestcyp51Aexpression, anAft1transposon was found inserted 370 bp upstream of the start codon of thecyp51Agene, an integration location never previously demonstrated inAspergillus. Two transcription start sites were identified at 49 and 136 bp upstream of the start codon. The role of theAft1transposon, if any, in modulatingcyp51Aexpression remains to be established. Increased mRNA expression of the transportersAfuMDR1andAfuMDR4also was demonstrated in some isolates, which could contribute to azole resistance or simply represent a stress response. The diversity of confirmed and possible azole resistance mechanisms demonstrated in a single series of isogenic isolates is remarkable, indicating the ability ofA. fumigatusto adapt in the clinical setting.

Development of a simple method for the determination of single nucleotide polymorphisms

2010 ◽  
Vol 34 (8) ◽  
pp. S75-S75
Author(s):  
Weifeng Zhu ◽  
Zhuoqi Liu ◽  
Daya Luo ◽  
Xinyao Wu ◽  
Fusheng Wan
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Simple Method ◽  
Single Nucleotide

Sex Differences in Childhood Associations between DNA Markers and General Cognitive Ability

2007 ◽  
Vol 28 (3) ◽  
pp. 161-164 ◽  
Author(s):  
Rosalind Arden ◽  
Nicole Harlaar ◽  
Robert Plomin
Keyword(s):  
Sex Differences ◽  
Single Nucleotide Polymorphisms ◽  
Cognitive Ability ◽  
Dna Markers ◽  
Community Sample ◽  
Nucleotide Polymorphisms ◽  
General Cognitive Ability ◽  
Single Nucleotide ◽  
The Difference

Abstract. An association between intelligence at age 7 and a set of five single-nucleotide polymorphisms (SNPs) has been identified and replicated. We used this composite SNP set to investigate whether the associations differ between boys and girls for general cognitive ability at ages 2, 3, 4, 7, 9, and 10 years. In a longitudinal community sample of British twins aged 2-10 (n > 4,000 individuals), we found that the SNP set is more strongly associated with intelligence in males than in females at ages 7, 9, and 10 and the difference is significant at 10. If this finding replicates in other studies, these results will constitute the first evidence of the same autosomal genes acting differently on intelligence in the two sexes.

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