A Comprehensive Analysis of the Lipidomic Signatures in <i>Rhizopus delemar</i>
Certain species of Mucorales have been identified as causative agents of mucormycosis, a rare yet often lethal fungal infection. Notably, these fungi exhibit intrinsic resistance to common azole drugs, which target lipids. Given the pivotal role of lipids in drug resistance and their contribution to...
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MDPI AG
2024-11-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/10/11/760 |
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| author | Basharat Ali Anshu Chauhan Mohit Kumar Praveen Kumar Hans Carolus Celia Lobo Romero Rudy Vergauwen Ashutosh Singh Atanu Banerjee Amresh Prakash Shivaprakash M. Rudramurthy Patrick Van Dijck Ashraf S. Ibrahim Rajendra Prasad |
| author_facet | Basharat Ali Anshu Chauhan Mohit Kumar Praveen Kumar Hans Carolus Celia Lobo Romero Rudy Vergauwen Ashutosh Singh Atanu Banerjee Amresh Prakash Shivaprakash M. Rudramurthy Patrick Van Dijck Ashraf S. Ibrahim Rajendra Prasad |
| author_sort | Basharat Ali |
| collection | DOAJ |
| description | Certain species of Mucorales have been identified as causative agents of mucormycosis, a rare yet often lethal fungal infection. Notably, these fungi exhibit intrinsic resistance to common azole drugs, which target lipids. Given the pivotal role of lipids in drug resistance and their contribution to innate resistance to azoles, this study provides a comprehensive overview of key lipid classes, including sphingolipids (SLs), glycerophospholipids (GPLs), and sterols, in <i>Rhizopus delemar</i> 99-880, a well-characterized reference strain among Mucorales. Using shotgun lipidomics as well as liquid- and gas-chromatography-based mass spectrometric analyses, we identified the lipid intermediates and elucidated the biosynthetic pathways of SLs, PGLs, and sterols. The acidic SLs were not found, probably because the acidic branch of the SL biosynthesis pathway terminates at α-hydroxy phytoceramides, as evident by their high abundance. Intermediates in the neutral SL pathway incorporated higher levels of 16:0 fatty acid compared to other pathogenic fungi. A strikingly high phosphatidylethanolamine (PE)/phosphatdylcholine (PC) ratio was observed among GPLs. Ergosterol remains the major sterol, similar to other fungi, and our analysis confirms the existence of alternate ergosterol biosynthesis pathways. The total lipidomic profile of <i>R. delemar</i> 99-880 offers insights into its lipid metabolism and potential implications for studying pathogenesis and drug resistance mechanisms. |
| format | Article |
| id | doaj-art-55dd50fbfb1c41e3b24a5480a9a837b5 |
| institution | OA Journals |
| issn | 2309-608X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj-art-55dd50fbfb1c41e3b24a5480a9a837b52025-08-20T02:04:58ZengMDPI AGJournal of Fungi2309-608X2024-11-01101176010.3390/jof10110760A Comprehensive Analysis of the Lipidomic Signatures in <i>Rhizopus delemar</i>Basharat Ali0Anshu Chauhan1Mohit Kumar2Praveen Kumar3Hans Carolus4Celia Lobo Romero5Rudy Vergauwen6Ashutosh Singh7Atanu Banerjee8Amresh Prakash9Shivaprakash M. Rudramurthy10Patrick Van Dijck11Ashraf S. Ibrahim12Rajendra Prasad13Amity Institute of Integrative Science and Health, Amity University Gurugram, Gurugram 122413, IndiaAmity Institute of Integrative Science and Health, Amity University Gurugram, Gurugram 122413, IndiaYeast Biofuel Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, IndiaAmity Institute of Integrative Science and Health, Amity University Gurugram, Gurugram 122413, IndiaLaboratory of Molecular Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, BelgiumLaboratory of Molecular Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, BelgiumLaboratory of Molecular Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, BelgiumDepartment of Biochemistry, University of Lucknow, Lucknow 226007, IndiaAmity Institute of Integrative Science and Health, Amity University Gurugram, Gurugram 122413, IndiaAmity Institute of Integrative Science and Health, Amity University Gurugram, Gurugram 122413, IndiaDepartment of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, IndiaLaboratory of Molecular Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, BelgiumDivision of Infectious Diseases, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USAAmity Institute of Integrative Science and Health, Amity University Gurugram, Gurugram 122413, IndiaCertain species of Mucorales have been identified as causative agents of mucormycosis, a rare yet often lethal fungal infection. Notably, these fungi exhibit intrinsic resistance to common azole drugs, which target lipids. Given the pivotal role of lipids in drug resistance and their contribution to innate resistance to azoles, this study provides a comprehensive overview of key lipid classes, including sphingolipids (SLs), glycerophospholipids (GPLs), and sterols, in <i>Rhizopus delemar</i> 99-880, a well-characterized reference strain among Mucorales. Using shotgun lipidomics as well as liquid- and gas-chromatography-based mass spectrometric analyses, we identified the lipid intermediates and elucidated the biosynthetic pathways of SLs, PGLs, and sterols. The acidic SLs were not found, probably because the acidic branch of the SL biosynthesis pathway terminates at α-hydroxy phytoceramides, as evident by their high abundance. Intermediates in the neutral SL pathway incorporated higher levels of 16:0 fatty acid compared to other pathogenic fungi. A strikingly high phosphatidylethanolamine (PE)/phosphatdylcholine (PC) ratio was observed among GPLs. Ergosterol remains the major sterol, similar to other fungi, and our analysis confirms the existence of alternate ergosterol biosynthesis pathways. The total lipidomic profile of <i>R. delemar</i> 99-880 offers insights into its lipid metabolism and potential implications for studying pathogenesis and drug resistance mechanisms.https://www.mdpi.com/2309-608X/10/11/760mucormycosisdrug resistanceposaconazoleamphotericin Bsphingolipidsphospholipids |
| spellingShingle | Basharat Ali Anshu Chauhan Mohit Kumar Praveen Kumar Hans Carolus Celia Lobo Romero Rudy Vergauwen Ashutosh Singh Atanu Banerjee Amresh Prakash Shivaprakash M. Rudramurthy Patrick Van Dijck Ashraf S. Ibrahim Rajendra Prasad A Comprehensive Analysis of the Lipidomic Signatures in <i>Rhizopus delemar</i> Journal of Fungi mucormycosis drug resistance posaconazole amphotericin B sphingolipids phospholipids |
| title | A Comprehensive Analysis of the Lipidomic Signatures in <i>Rhizopus delemar</i> |
| title_full | A Comprehensive Analysis of the Lipidomic Signatures in <i>Rhizopus delemar</i> |
| title_fullStr | A Comprehensive Analysis of the Lipidomic Signatures in <i>Rhizopus delemar</i> |
| title_full_unstemmed | A Comprehensive Analysis of the Lipidomic Signatures in <i>Rhizopus delemar</i> |
| title_short | A Comprehensive Analysis of the Lipidomic Signatures in <i>Rhizopus delemar</i> |
| title_sort | comprehensive analysis of the lipidomic signatures in i rhizopus delemar i |
| topic | mucormycosis drug resistance posaconazole amphotericin B sphingolipids phospholipids |
| url | https://www.mdpi.com/2309-608X/10/11/760 |
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