H3K4 methylation regulates development, DNA repair, and virulence in Mucorales
Abstract Mucorales are basal fungi that opportunistically cause a potentially fatal infection known as mucormycosis (black fungus disease), which poses a significant threat to human health due to its high mortality rate and its recent association with SARS-CoV-2 infections. On the other hand, histon...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | IMA Fungus |
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| Online Access: | https://doi.org/10.1186/s43008-023-00136-3 |
| _version_ | 1797259098900660224 |
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| author | Macario Osorio-Concepción Carlos Lax Damaris Lorenzo-Gutiérrez José Tomás Cánovas-Márquez Ghizlane Tahiri Eusebio Navarro Ulrike Binder Francisco Esteban Nicolás Victoriano Garre |
| author_facet | Macario Osorio-Concepción Carlos Lax Damaris Lorenzo-Gutiérrez José Tomás Cánovas-Márquez Ghizlane Tahiri Eusebio Navarro Ulrike Binder Francisco Esteban Nicolás Victoriano Garre |
| author_sort | Macario Osorio-Concepción |
| collection | DOAJ |
| description | Abstract Mucorales are basal fungi that opportunistically cause a potentially fatal infection known as mucormycosis (black fungus disease), which poses a significant threat to human health due to its high mortality rate and its recent association with SARS-CoV-2 infections. On the other hand, histone methylation is a regulatory mechanism with pleiotropic effects, including the virulence of several pathogenic fungi. However, the role of epigenetic changes at the histone level never has been studied in Mucorales. Here, we dissected the functional role of Set1, a histone methyltransferase that catalyzes the methylation of H3K4, which is associated with the activation of gene transcription and virulence. A comparative analysis of the Mucor lusitanicus genome (previously known as Mucor circinelloides f. lusitanicus) identified only one homolog of Set1 from Candida albicans and Saccharomyces cerevisiae that contains the typical SET domain. Knockout strains in the gene set1 lacked H3K4 monomethylation, dimethylation, and trimethylation enzymatic activities. These strains also showed a significant reduction in vegetative growth and sporulation. Additionally, set1 null strains were more sensitive to SDS, EMS, and UV light, indicating severe impairment in the repair process of the cell wall and DNA lesions and a correlation between Set1 and these processes. During pathogen-host interactions, strains lacking the set1 gene exhibited shortened polar growth within the phagosome and attenuated virulence both in vitro and in vivo. Our findings suggest that the histone methyltransferase Set1 coordinates several cell processes related to the pathogenesis of M. lusitanicus and may be an important target for future therapeutic strategies against mucormycosis. |
| first_indexed | 2024-04-24T23:04:02Z |
| format | Article |
| id | doaj.art-b9f413d3edd7414bab1b37a7c36dfcb4 |
| institution | Directory Open Access Journal |
| issn | 2210-6359 |
| language | English |
| last_indexed | 2024-04-24T23:04:02Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | IMA Fungus |
| spelling | doaj.art-b9f413d3edd7414bab1b37a7c36dfcb42024-03-17T12:33:51ZengBMCIMA Fungus2210-63592024-03-0115111510.1186/s43008-023-00136-3H3K4 methylation regulates development, DNA repair, and virulence in MucoralesMacario Osorio-Concepción0Carlos Lax1Damaris Lorenzo-Gutiérrez2José Tomás Cánovas-Márquez3Ghizlane Tahiri4Eusebio Navarro5Ulrike Binder6Francisco Esteban Nicolás7Victoriano Garre8Departamento de Genética y Microbiología, Facultad de Biología, Universidad de MurciaDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de MurciaDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de MurciaDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de MurciaDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de MurciaDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de MurciaInstitute of Hygiene and Medical Microbiology, Medical University of InnsbruckDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de MurciaDepartamento de Genética y Microbiología, Facultad de Biología, Universidad de MurciaAbstract Mucorales are basal fungi that opportunistically cause a potentially fatal infection known as mucormycosis (black fungus disease), which poses a significant threat to human health due to its high mortality rate and its recent association with SARS-CoV-2 infections. On the other hand, histone methylation is a regulatory mechanism with pleiotropic effects, including the virulence of several pathogenic fungi. However, the role of epigenetic changes at the histone level never has been studied in Mucorales. Here, we dissected the functional role of Set1, a histone methyltransferase that catalyzes the methylation of H3K4, which is associated with the activation of gene transcription and virulence. A comparative analysis of the Mucor lusitanicus genome (previously known as Mucor circinelloides f. lusitanicus) identified only one homolog of Set1 from Candida albicans and Saccharomyces cerevisiae that contains the typical SET domain. Knockout strains in the gene set1 lacked H3K4 monomethylation, dimethylation, and trimethylation enzymatic activities. These strains also showed a significant reduction in vegetative growth and sporulation. Additionally, set1 null strains were more sensitive to SDS, EMS, and UV light, indicating severe impairment in the repair process of the cell wall and DNA lesions and a correlation between Set1 and these processes. During pathogen-host interactions, strains lacking the set1 gene exhibited shortened polar growth within the phagosome and attenuated virulence both in vitro and in vivo. Our findings suggest that the histone methyltransferase Set1 coordinates several cell processes related to the pathogenesis of M. lusitanicus and may be an important target for future therapeutic strategies against mucormycosis.https://doi.org/10.1186/s43008-023-00136-3MucormycosisSet1PathogenesisHistone methyltransferaseMucor |
| spellingShingle | Macario Osorio-Concepción Carlos Lax Damaris Lorenzo-Gutiérrez José Tomás Cánovas-Márquez Ghizlane Tahiri Eusebio Navarro Ulrike Binder Francisco Esteban Nicolás Victoriano Garre H3K4 methylation regulates development, DNA repair, and virulence in Mucorales IMA Fungus Mucormycosis Set1 Pathogenesis Histone methyltransferase Mucor |
| title | H3K4 methylation regulates development, DNA repair, and virulence in Mucorales |
| title_full | H3K4 methylation regulates development, DNA repair, and virulence in Mucorales |
| title_fullStr | H3K4 methylation regulates development, DNA repair, and virulence in Mucorales |
| title_full_unstemmed | H3K4 methylation regulates development, DNA repair, and virulence in Mucorales |
| title_short | H3K4 methylation regulates development, DNA repair, and virulence in Mucorales |
| title_sort | h3k4 methylation regulates development dna repair and virulence in mucorales |
| topic | Mucormycosis Set1 Pathogenesis Histone methyltransferase Mucor |
| url | https://doi.org/10.1186/s43008-023-00136-3 |
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