This study initially aimed at investigating the occurrence of azole resistance among Candida spp. from animals and analyzing the involvement of efflux pumps in the resistance phenomenon. Then, the dynamics of antifungal resistance was assessed, by comparing the antifungal epidemiological cutoff values (ECVs) against C. albicans and C. tropicalis from humans and animals. Fifty azole-resistant isolates (24 C. albicans, 24 C. tropicalis; 2 C. parapsilosis sensu lato) were submitted to the efflux pump inhibition assay with promethazine and significant MIC reductions were observed for fluconazole (2 to 250-fold) and itraconazole (16 to 4000-fold). Then, the antifungal ECVs against C. albicans and C. tropicalis from human and animal isolates were compared. Fluconazole, itraconazole and voriconazole ECVs against human isolates were lower than those against animal isolates. Based on the antifungal ECVs against human isolates, only 33.73%, 50.39% and 63.53% of C. albicans and 52.23%, 61.85% and 55.17% of C. tropicalis from animals were classified as wild-type for fluconazole, itraconazole and voriconazole, respectively. Therefore, efflux-mediated mechanisms are involved in azole resistance among Candida spp. from animals and this phenomenon seems to emerge in animal-associated niches, pointing to the existence of environmental drivers of resistance and highlighting the importance of the One Health approach to control it.
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http://dx.doi.org/10.1093/mmy/myz135 | DOI Listing |
Mycopathologia
December 2024
Department of Medical Microbiology, Faculty of Medicine, University of Debrecen, Nagyerdei Krt. 98., Debrecen, 4032, Hungary.
The sudden emergence of multidrug- and pan-resistant Candida auris isolates, combined with limited treatment options, poses significant global challenges in healthcare settings. Combination based therapies are promising alternative options to overcome C. auris related infections, where echinocandin and isavuconazole (ISA) combinations may be an interesting and promising approach.
View Article and Find Full Text PDFElife
December 2024
Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, United States.
Inhibition of Bruton's tyrosine kinase (BTK) has proven to be highly effective in the treatment of B-cell malignancies such as chronic lymphocytic leukemia (CLL), autoimmune disorders, and multiple sclerosis. Since the approval of the first BTK inhibitor (BTKi), Ibrutinib, several other inhibitors including Acalabrutinib, Zanubrutinib, Tirabrutinib, and Pirtobrutinib have been clinically approved. All are covalent active site inhibitors, with the exception of the reversible active site inhibitor Pirtobrutinib.
View Article and Find Full Text PDFJ Fungi (Basel)
December 2024
Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Noria Alta s/n, col. Noria Alta, Guanajuato C.P. 36050, Mexico.
This review explores current advancements and challenges in antifungal therapies amid rising fungal infections, particularly in immunocompromised patients. We detail the limitations of existing antifungal classes-azoles, echinocandins, polyenes, and flucytosine-in managing systemic infections and the urgent need for alternative solutions. With the increasing incidence of resistance pathogens, such as and , we assess emerging antifungal agents, including Ibrexafungerp, T-2307, and N'-Phenylhydrazides, which target diverse fungal cell mechanisms.
View Article and Find Full Text PDFJ Fungi (Basel)
November 2024
Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin 9016, New Zealand.
is intrinsically resistant to the widely used antifungal fluconazole, and therapeutic failure can result from acquired resistance to voriconazole, the primary treatment for invasive aspergillosis. The molecular basis of substrate specificity and innate and acquired resistance of to azole drugs were addressed using crystal structures, molecular models, and expression in of the sterol 14α-demethylase isoforms AfCYP51A and AfCYP51B targeted by azole drugs, together with their cognate reductase AfCPRA2 and AfERG6 (sterol 24-C-methyltransferase). As predicted by molecular modelling, functional expression of CYP51A and B required eburicol and not lanosterol.
View Article and Find Full Text PDFJ Fungi (Basel)
November 2024
Department of Biosciences and Biotechnologies, Graduate School of Bioresources and Bioenvironment Sciences, Kyushu University, 744 W5-674, Motooka Nishi-ku, Fukuoka 819-0395, Japan.
(), the second most prevalent Candida pathogen globally, has emerged as a major clinical threat due to its ability to develop high-level azole resistance. In this study, two new 5,6-dihydrotetrazolo[1,5-]quinazoline derivatives ( and ) were synthesized and characterized using IR, LC-MS, H, and C NMR spectra. Along with 13 previously reported analogues, these compounds underwent in vitro antifungal testing against clinical isolates using a serial dilution method (0.
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