Data Sheet 1_Intrinsic resistance to short-tailed azoles in the basal fungus Mucor lusitanicus: functional analysis of Cyp51 isoforms and amino acid substitutions.docx
Introduction<p>The basal fungus Mucor lusitanicus (Mlu) is a cause of mucormycosis, with limited treatment options due to intrinsic resistance to short-tailed azoles (fluconazole, voriconazole) and echinocandins. In silico analysis identified amino-acid-substitutions Y129F and V293A in the sub...
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| author | K. Rosam (22687364) |
| author2 | M. V. Keniya (22687367) L.-M. Zenz (22687370) C. Müller (2693209) B. Sarg (22687373) M. Stojanovic (15235538) U. Binder (22687376) B. C. Monk (22687379) M. Lackner (3971021) |
| author2_role | author author author author author author author author |
| author_facet | K. Rosam (22687364) M. V. Keniya (22687367) L.-M. Zenz (22687370) C. Müller (2693209) B. Sarg (22687373) M. Stojanovic (15235538) U. Binder (22687376) B. C. Monk (22687379) M. Lackner (3971021) |
| author_role | author |
| dc.creator.none.fl_str_mv | K. Rosam (22687364) M. V. Keniya (22687367) L.-M. Zenz (22687370) C. Müller (2693209) B. Sarg (22687373) M. Stojanovic (15235538) U. Binder (22687376) B. C. Monk (22687379) M. Lackner (3971021) |
| dc.date.none.fl_str_mv | 2025-11-26T06:33:27Z |
| dc.identifier.none.fl_str_mv | 10.3389/fmicb.2025.1702408.s001 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Data_Sheet_1_Intrinsic_resistance_to_short-tailed_azoles_in_the_basal_fungus_Mucor_lusitanicus_functional_analysis_of_Cyp51_isoforms_and_amino_acid_substitutions_docx/30718643 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Microbiology azole AMR (antimicrobial resistance) mucormycoses mucormycetes lanosterol 14α demethylase Saccharomyces cerevisiae heterologous expression GMO (genetically modified organism) |
| dc.title.none.fl_str_mv | Data Sheet 1_Intrinsic resistance to short-tailed azoles in the basal fungus Mucor lusitanicus: functional analysis of Cyp51 isoforms and amino acid substitutions.docx |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | Introduction<p>The basal fungus Mucor lusitanicus (Mlu) is a cause of mucormycosis, with limited treatment options due to intrinsic resistance to short-tailed azoles (fluconazole, voriconazole) and echinocandins. In silico analysis identified amino-acid-substitutions Y129F and V293A in the substrate-binding pocket of sterol-14α-demethylase (Cyp51, Erg11) isoform F5 as potential resistance mechanisms.</p>Methods<p>This hypothesis has been experimentally tested for M. lusitanicus by expressing its Cyp51 isoforms (MluCyp51-F1, MluCyp51-F5) and modified MluCyp51-F5 variants (F129Y, A293V, F129Y A293V) with/without their cognate NADPH-cytochrome-P450-reductase (MluCPR) in Saccharomyces cerevisiae.</p>Results<p>Strains expressing MluCyp51 isoforms +/− MluCPR showed expression levels of 38–69% compared to an overexpressed Erg11 control. Susceptibility assays confirmed that MluCyp51-F5 confers intrinsic resistance to short-tailed azoles, while substitutions F129Y, A293V, or both restored susceptibility. Growth- and susceptibility-assays revealed that the MluCyp51-F1 + CPR construct had a voriconazole MIC of 0.5 μM, while MluCyp51-F5 + CPR had a MIC of 11.5 μM, with no changes in growth rate or ergosterol composition at 1.0 μM voriconazole. Susceptibility to long-tailed azoles (e.g., posaconazole) remained unchanged for both isoforms.</p>Discussion<p>These findings demonstrate the functional expression of MluCyp51-F1 and MluCyp51-F5 isoforms in a phylogenetically distant host and confirm that conserved substitutions Y129F and V293A in MluCyp51-F5 confer intrinsic resistance to short-tailed azoles in M. lusitanicus.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_1fabc94533bbba0aabee99bd905e4e7b |
| identifier_str_mv | 10.3389/fmicb.2025.1702408.s001 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30718643 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Data Sheet 1_Intrinsic resistance to short-tailed azoles in the basal fungus Mucor lusitanicus: functional analysis of Cyp51 isoforms and amino acid substitutions.docxK. Rosam (22687364)M. V. Keniya (22687367)L.-M. Zenz (22687370)C. Müller (2693209)B. Sarg (22687373)M. Stojanovic (15235538)U. Binder (22687376)B. C. Monk (22687379)M. Lackner (3971021)MicrobiologyazoleAMR (antimicrobial resistance)mucormycosesmucormyceteslanosterol 14α demethylaseSaccharomyces cerevisiaeheterologous expressionGMO (genetically modified organism)Introduction<p>The basal fungus Mucor lusitanicus (Mlu) is a cause of mucormycosis, with limited treatment options due to intrinsic resistance to short-tailed azoles (fluconazole, voriconazole) and echinocandins. In silico analysis identified amino-acid-substitutions Y129F and V293A in the substrate-binding pocket of sterol-14α-demethylase (Cyp51, Erg11) isoform F5 as potential resistance mechanisms.</p>Methods<p>This hypothesis has been experimentally tested for M. lusitanicus by expressing its Cyp51 isoforms (MluCyp51-F1, MluCyp51-F5) and modified MluCyp51-F5 variants (F129Y, A293V, F129Y A293V) with/without their cognate NADPH-cytochrome-P450-reductase (MluCPR) in Saccharomyces cerevisiae.</p>Results<p>Strains expressing MluCyp51 isoforms +/− MluCPR showed expression levels of 38–69% compared to an overexpressed Erg11 control. Susceptibility assays confirmed that MluCyp51-F5 confers intrinsic resistance to short-tailed azoles, while substitutions F129Y, A293V, or both restored susceptibility. Growth- and susceptibility-assays revealed that the MluCyp51-F1 + CPR construct had a voriconazole MIC of 0.5 μM, while MluCyp51-F5 + CPR had a MIC of 11.5 μM, with no changes in growth rate or ergosterol composition at 1.0 μM voriconazole. Susceptibility to long-tailed azoles (e.g., posaconazole) remained unchanged for both isoforms.</p>Discussion<p>These findings demonstrate the functional expression of MluCyp51-F1 and MluCyp51-F5 isoforms in a phylogenetically distant host and confirm that conserved substitutions Y129F and V293A in MluCyp51-F5 confer intrinsic resistance to short-tailed azoles in M. lusitanicus.</p>2025-11-26T06:33:27ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.3389/fmicb.2025.1702408.s001https://figshare.com/articles/dataset/Data_Sheet_1_Intrinsic_resistance_to_short-tailed_azoles_in_the_basal_fungus_Mucor_lusitanicus_functional_analysis_of_Cyp51_isoforms_and_amino_acid_substitutions_docx/30718643CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/307186432025-11-26T06:33:27Z |
| spellingShingle | Data Sheet 1_Intrinsic resistance to short-tailed azoles in the basal fungus Mucor lusitanicus: functional analysis of Cyp51 isoforms and amino acid substitutions.docx K. Rosam (22687364) Microbiology azole AMR (antimicrobial resistance) mucormycoses mucormycetes lanosterol 14α demethylase Saccharomyces cerevisiae heterologous expression GMO (genetically modified organism) |
| status_str | publishedVersion |
| title | Data Sheet 1_Intrinsic resistance to short-tailed azoles in the basal fungus Mucor lusitanicus: functional analysis of Cyp51 isoforms and amino acid substitutions.docx |
| title_full | Data Sheet 1_Intrinsic resistance to short-tailed azoles in the basal fungus Mucor lusitanicus: functional analysis of Cyp51 isoforms and amino acid substitutions.docx |
| title_fullStr | Data Sheet 1_Intrinsic resistance to short-tailed azoles in the basal fungus Mucor lusitanicus: functional analysis of Cyp51 isoforms and amino acid substitutions.docx |
| title_full_unstemmed | Data Sheet 1_Intrinsic resistance to short-tailed azoles in the basal fungus Mucor lusitanicus: functional analysis of Cyp51 isoforms and amino acid substitutions.docx |
| title_short | Data Sheet 1_Intrinsic resistance to short-tailed azoles in the basal fungus Mucor lusitanicus: functional analysis of Cyp51 isoforms and amino acid substitutions.docx |
| title_sort | Data Sheet 1_Intrinsic resistance to short-tailed azoles in the basal fungus Mucor lusitanicus: functional analysis of Cyp51 isoforms and amino acid substitutions.docx |
| topic | Microbiology azole AMR (antimicrobial resistance) mucormycoses mucormycetes lanosterol 14α demethylase Saccharomyces cerevisiae heterologous expression GMO (genetically modified organism) |