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8 results on '"Hokken, M.W.J."'

2. The Transcriptome Response to Azole Compounds in Aspergillus fumigatus Shows Differential Gene Expression across Pathways Essential for Azole Resistance and Cell Survival.

Author

Hokken, M.W.J., Coolen, J.P.M., Steenbreker, Hilbert, Zoll, J., Baltussen, T.J.H., Verweij, P.E., Melchers, W.J.G., Hokken, M.W.J., Coolen, J.P.M., Steenbreker, Hilbert, Zoll, J., Baltussen, T.J.H., Verweij, P.E., and Melchers, W.J.G.

Abstract

Contains fulltext : 296047.pdf (Publisher’s version ) (Open Access), The opportunistic pathogen Aspergillus fumigatus is found on all continents and thrives in soil and agricultural environments. Its ability to readily adapt to novel environments and to produce billions of spores led to the spread of azole-resistant A. fumigatus across the globe, posing a threat to many immunocompromised patients, including critically ill patients with severe influenza or COVID-19. In our study, we sought to compare the adaptational response to azoles from A. fumigatus isolates that differ in azole susceptibility and genetic background. To gain more insight into how short-term adaptation to stressful azole compounds is managed through gene expression, we conducted an RNA-sequencing study on the response of A. fumigatus to itraconazole and the newest clinically approved azole, isavuconazole. We observed many similarities in ergosterol biosynthesis up-regulation across isolates, with the exception of the pan-azole-resistant isolate, which showed very little differential regulation in comparison to other isolates. Additionally, we found differential regulation of membrane efflux transporters, secondary metabolites, iron metabolism, and various stress response and cell signaling mechanisms.

Published
2023

4. Resistance profiling of Aspergillus fumigatus to olorofim indicates absence of intrinsic resistance and unveils the molecular mechanisms of acquired olorofim resistance

Author

Buil, J.B., Oliver, Jason D., Law, D., Baltussen, T.J.H., Zoll, J., Hokken, M.W.J., Tehupeiory-Kooreman, M.C., Melchers, W.J.G., Birch, M., Verweij, P.E., Buil, J.B., Oliver, Jason D., Law, D., Baltussen, T.J.H., Zoll, J., Hokken, M.W.J., Tehupeiory-Kooreman, M.C., Melchers, W.J.G., Birch, M., and Verweij, P.E.

Abstract

Item does not contain fulltext

Published
2022

5. Hmg1 Gene Mutation Prevalence in Triazole-Resistant Aspergillus fumigatus Clinical Isolates

Author

Resendiz-Sharpe, Agustin, Hokken, M.W.J., Mercier, Toine, Merckx, Rita, Verhagen, Kamiel, Dewitte, Lisa, Melchers, W.J.G., Verweij, P.E., Maertens, Johan, Lagrou, Katrien, Resendiz-Sharpe, Agustin, Hokken, M.W.J., Mercier, Toine, Merckx, Rita, Verhagen, Kamiel, Dewitte, Lisa, Melchers, W.J.G., Verweij, P.E., Maertens, Johan, and Lagrou, Katrien

Abstract

Contains fulltext : 228702.pdf (publisher's version ) (Open Access)

Published
2020

6. Facilitators of adaptation and antifungal resistance mechanisms in clinically relevant fungi.

Author

Hokken, M.W.J., Zwaan, B.J., Melchers, W.J.G., Verweij, P.E., Hokken, M.W.J., Zwaan, B.J., Melchers, W.J.G., and Verweij, P.E.

Abstract

01 november 2019, Contains fulltext : 215617.pdf (publisher's version ) (Open Access), Opportunistic fungal pathogens can cause a diverse range of diseases in humans. The increasing rate of fungal infections caused by strains that are resistant to commonly used antifungals results in difficulty to treat diseases, with accompanying high mortality rates. Existing and newly emerging molecular resistance mechanisms rapidly spread in fungal populations and need to be monitored. Fungi exhibit a diversity of mechanisms to maintain physiological resilience and create genetic variation; processes which eventually lead to the selection and spread of resistant fungal pathogens. To prevent and anticipate this dispersion, the role of evolutionary factors that drive fungal adaptation should be investigated. In this review, we provide an overview of resistance mechanisms against commonly used antifungal compounds in the clinic and for which fungal resistance has been reported. Furthermore, we aim to summarize and elucidate potent generators of genetic variability across the fungal kingdom that aid adaptation to stressful environments. This knowledge can lead to recognizing potential niches that facilitate fast resistance development and can provide leads for new management strategies to battle the emerging resistant populations in the clinic and the environment.

Published
2019

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