Since the mid-1990s, a steady increase in the occurrence of itraconazole-resistant Aspergillus fumigatus isolates has been observed in clinical contexts, leading to therapeutic failure in the treatment of aspergillosis. This increase has been predominantly linked to a single allele of the cyp51A gene, termed TR/L98H, which is thought to have arisen through the use of agricultural azoles. Here, we investigated the current epidemiology of triazole-resistant A. fumigatus and underlying cyp51A mutations in clinical samples in Germany. From a total of 527 samples, 17 (3.2%) showed elevated MIC0 values (the lowest concentrations with no visible growth) for at least one of the three substances (itraconazole, voriconazole, and posaconazole) tested. The highest prevalence of resistant isolates was observed in cystic fibrosis patients (5.2%). Among resistant isolates, the TR/L98H mutation in cyp51A was the most prevalent, but isolates with the G54W and M220I substitutions and the novel F219C substitution were also found. The isolate with the G54W substitution was highly resistant to both itraconazole and posaconazole, while all others showed high-level resistance only to itraconazole. For the remaining six isolates, no mutations in cyp51A were found, indicating the presence of other mechanisms. With the exception of the strains carrying the F219C and M220I substitutions, many itraconazole-resistant strains also showed cross-resistance to voriconazole and posaconazole with moderately increased MIC0 values. In conclusion, the prevalence of azole-resistant A. fumigatus in our clinical test set is lower than that previously reported for other countries. Although the TR/L98H mutation frequently occurs among triazole-resistant strains in Germany, it is not the only resistance mechanism present.
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http://dx.doi.org/10.1128/AAC.00167-13 | DOI Listing |
Sci Rep
December 2024
Emerging Pathogens Institute, University of Florida, Gainesville, FL, 32611, USA.
This paper introduces a novel, compact plasma sterilization system, the Active Plasma Sterilizer (APS), for planetary protection space missions. The development of the APS system is done through iterative testing and design modifications aimed at addressing decontamination modalities for time and temperature, cleaning adhesive surfaces, and cleaning protocols beyond alcohol and bleach. Decontamination testing of Deinococcus radiodurans, Geobacillus stearothermophilus (spore forming bacteria), and Aspergillus fumigatus (fungi) was verified for the APS on relevant materials of 4 to 5 log reduction up to complete killing in 45 min or less.
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)
December 2024
Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand.
Due to the high morbidity and mortality rates of invasive aspergillosis (IA) and the importance of early IA detection for successful treatment and subsequent outcome, this study aimed to determine a time course of detectable antigen in a mouse model of IA and correlate it with tissue invasion by using two novel monoclonal antibodies, 1D2 and 4E4, that can be used to detect the -derived glycoproteins. Immunocompromised mice were randomly divided into five groups: uninfected control, and inoculation with conidia from , , and . Conidia (2 × 10 cells/mL) were administered intravenously via tail vein injection.
View Article and Find Full Text PDFJ Fungi (Basel)
November 2024
Department of Molecular Biotechnology and Microbiology, Institute of Biotechnology, Faculty of Science and Technology, University of Debrecen, H-4032 Debrecen, Hungary.
The importance of manganese superoxide dismutase (Mn-SOD), an evolutionarily ancient metalloenzyme that maintains the integrity and function of mitochondria, was studied in oxidative stress-treated cultures. Deletion of the Mn-SOD gene () increased both the menadione sodium bisulfite (MSB)-elicited oxidative stress and the deferiprone (DFP)-induced iron limitation stress sensitivity of the strain. Moreover, DFP treatment enhanced the MSB sensitivity of both the gene deletion mutant and the reference strain.
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.
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