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Description
Opportunistic pathogenic fungi cause infectious fungal disease with extremely high mortality rates, especially in immune-compromised patients [1]. Antifungal resistance and multi-drug resistance have emerged against the limited number of clinically used antifungals. Because of the high HIV/AIDS incidence in Sub-Saharan Africa [2], anti-fungal drug resistance is specifically of concern; therefore, there is an urgent need to develop novel therapies.
In this study, sterol C24-methyltransferase (SMT) has been identified as a novel target for anti-fungal drug development. An expression vector library was prepared with SMT genes from four opportunistic pathogenic fungi, heterologously expressed in Escherichia coli and the SMT proteins purified with affinity chromatography. The SMT from Candida albicans was crystallised and diffraction data was collected at the Diamond Light Source synchrotron.
Expression of truncated SMT genes from all four fungi was successful, and the SMT from C. albicans was successfully purified and crystallised; however, diffraction was only observed at low resolution (~7Å). Purification of the SMTs from the other three pathogens is ongoing, and crystallisation of the C. albicans SMT is currently being optimised.
[1] Denning DW (2024) Global incidence and mortality of severe fungal disease. Lancet Infectious Diseases. 24(7):e428-e438.
[2] Dos Santos Abrantes PM, McArthur CP & Africa CWJ (2014). Multi-drug resistant oral Candida species isolated from HIV-positive patients in South Africa and Cameroon. Diagnostic Microbiology and Infectious Disease. 79(2), 222–227.
