We determined the abilities of 10 technologies to detect and quantify a common drug-resistant mutant of human immunodeficiency virus type 1 (lysine to asparagine at codon 103 of the reverse transcriptase) using a blinded test panel containing mutant-wild-type mixtures ranging from 0.01% to 100% mutant. Two technologies, allele-specific reverse transcriptase PCR and a Ty1HRT yeast system, could quantify the mutant down to 0.1 to 0.4%. These technologies should help define the impact of low-frequency drug-resistant mutants on response to antiretroviral therapy.
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http://dx.doi.org/10.1128/JCM.00449-06 | DOI Listing |
Nat Commun
January 2025
Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Multidrug resistance in the pathogenic fungus Candida glabrata is a growing global threat. Here, we study mechanisms of multidrug resistance in this pathogen. Exposure of C.
View Article and Find Full Text PDFViruses
January 2025
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
Second-generation integrase strand transfer inhibitors (INSTIs) are strongly recommended for people living with HIV-1 (PLWH). The emergence of resistance to second-generation INSTIs has been infrequent and has not yet been a major issue in high-income countries. However, the delayed rollouts of these INSTIs in low- to middle-income countries during the COVID-19 pandemic combined with increased transmission of drug-resistant mutants worldwide are leading to an increase in INSTI resistance.
View Article and Find Full Text PDFMolecules
January 2025
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Epigenetic abnormalities play a critical role in colon carcinogenesis, making them a promising target for therapeutic interventions. In this study, we demonstrated that curcumin reduces colon cancer cell survival and that a decrease in lysine methylation was involved in such an effect. This correlated with the downregulation of methyltransferases EZH2, MLL1, and G9a, in both wild-type p53 (wtp53) HCT116 cells and mutant p53 (mutp53) SW480 cells, as well as SET7/9 specifically in wtp53 HCT116 cells.
View Article and Find Full Text PDFMicroorganisms
December 2024
Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
Antimicrobial resistance (AMR) represents a critical global health threat, and a thorough understanding of resistance mechanisms in is needed to guide effective treatment interventions. This review explores recent advances for investigating AMR in , including machine learning for resistance pattern analysis, laboratory evolution to generate resistant mutants, mutant library construction, and genome sequencing for in-depth characterization. Key resistance mechanisms are discussed, including drug inactivation, target modification, altered transport, and metabolic adaptation.
View Article and Find Full Text PDFSci Rep
January 2025
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Genotype-informed anticancer therapies such as BRAF inhibitors can show remarkable clinical efficacy in BRAF-mutant melanoma; however, drug resistance poses a major hurdle to successful cancer treatment. Many resistance events to targeted therapies have been identified, suggesting a complex path to improve therapeutics. Here, we showed the utility of a piggyBac transposon activation mutagenesis screen for the efficient identification of genes that are resistant to BRAF inhibition in melanoma.
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