We tested the hypothesis that the time course of the evolution of antifungal drug resistance depends on the ploidy of the fungus. The experiments were designed to measure the initial response to the selection imposed by the antifungal drug fluconazole up to and including the fixation of the first resistance mutation in populations of Saccharomyces cerevisiae. Under conditions of low drug concentration, mutations in the genes PDR1 and PDR3, which regulate the ABC transporters implicated in resistance to fluconazole, are favored. In this environment, diploid populations of defined size consistently became fixed for a resistance mutation sooner than haploid populations. Experiments manipulating population sizes showed that this advantage of diploids was due to increased mutation availability relative to that of haploids; in effect, diploids have twice the number of mutational targets as haploids and hence have a reduced waiting time for mutations to occur. Under conditions of high drug concentration, recessive mutations in ERG3, which result in resistance through altered sterol synthesis, are favored. In this environment, haploids consistently achieved resistance much sooner than diploids. When 29 haploid and 29 diploid populations were evolved for 100 generations in low drug concentration, the mutations fixed in diploid populations were all dominant, while the mutations fixed in haploid populations were either recessive (16 populations) or dominant (13 populations). Further, the spectrum of the 53 nonsynonymous mutations identified at the sequence level was different between haploids and diploids. These results fit existing theory on the relative abilities of haploids and diploids to adapt and suggest that the ploidy of the fungal pathogen has a strong impact on the evolution of fluconazole resistance.
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http://dx.doi.org/10.1534/genetics.104.033266 | DOI Listing |
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Department of Chemistry, Jamia Millia Islamia, New Delhi, India.
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View Article and Find Full Text PDFScientifica (Cairo)
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The global problem of infectious and deadly diseases caused by microbes such as candida and mycobacteria presents major scientific and medical challenges. Antimicrobial drug resistance is a rapidly growing problem with potentially devastating consequences. Various pathogens can cause skin infections, such as bacteria, fungi, and parasites.
View Article and Find Full Text PDFCurr Microbiol
January 2025
Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Poonamallee High Road, Chennai, Tamil Nadu, 600 077, India.
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View Article and Find Full Text PDFMethods Mol Biol
January 2025
Natural Products Laboratory, Institute of Biology Leiden, Leiden University, Leiden, The Netherlands.
Salicylic acid is a member of benzoic acid derivatives, a group of compounds which have a backbone of C6C1 consisting of one carboxyl group and one (or more) hydroxyl group(s) attached to the aromatic ring. Salicylic acid is a signaling compound in systemic acquired resistance (SAR). An increased level of salicylic acid is found in the plant after a fungi's attack, which further induces the accumulation of phytoalexins, low molecular weight defense compounds.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning, Guangxi 530004, China; Guangxi Zhuang Autonomous Region Engineering Research Center of Veterinary Biologics, Nanning, Guangxi 530004, China. Electronic address:
The application of hydrogels to drug delivery limited by the difficulty of encapsulating hydrophobic drugs; therefore, the development of novel composite hydrogels for the delivery of hydrophobic drugs is urgently needed. In this study, terbinafine hydrochloride/hydroxypropyl-β-cyclodextrin inclusion complexes (TFH/HP-β-CD ICs) were added to a Schiff base hydrogel matrix containing octenyl succinic anhydride-modified chitosan (OSA-CS) and sodium alginate (OIA) to prepare a TFH composite hydrogel (TFH GEL). The results revealed that the solubility of TFH in water within TFH/HP-β-CD IC reached 32.
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