The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in <i>Aspergillus fumigatus</i>
Histone demethylases govern diverse cellular processes, including growth, development, and secondary metabolism. In the present study, we investigated the functions of two lysine demethylases, KdmA and KdmB, in the opportunistic human pathogenic fungus <i>Aspergillus fumigatus</i>. Exper...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Journal of Fungi |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2309-608X/8/6/590 |
| _version_ | 1827659442151227392 |
|---|---|
| author | Yong-Ho Choi Min-Woo Lee Kwang-Soo Shin |
| author_facet | Yong-Ho Choi Min-Woo Lee Kwang-Soo Shin |
| author_sort | Yong-Ho Choi |
| collection | DOAJ |
| description | Histone demethylases govern diverse cellular processes, including growth, development, and secondary metabolism. In the present study, we investigated the functions of two lysine demethylases, KdmA and KdmB, in the opportunistic human pathogenic fungus <i>Aspergillus fumigatus</i>. Experiments with mutants harboring deletions of genes encoding KdmA (Δ<i>kdmA</i>) and KdmB (Δ<i>kdmB</i>) showed that KdmA is necessary for normal growth and proper conidiation, whereas KdmB negatively regulates vegetative growth and conidiation. In both mutant strains, tolerance to H<sub>2</sub>O<sub>2</sub> was significantly decreased, and the activities of both conidia-specific catalase (CatA) and mycelia-specific catalase (Cat1) were decreased. Both mutants had significantly increased sensitivity to the guanine nucleotide synthesis inhibitor 6-azauracil (6AU). The Δ<i>kdmA</i> mutant produced more gliotoxin (GT), but the virulence was not changed significantly in immunocompromised mice. In contrast, the production of GT and virulence were markedly reduced by the loss of <i>kdmB</i>. Comparative transcriptomic analyses revealed that the expression levels of developmental process-related genes and antioxidant activity-related genes were downregulated in both mutants. Taken together, we concluded that KdmA and KdmB have opposite roles in vegetative growth, asexual sporulation, and GT production. However, the two proteins were equally important for the development of resistance to 6AU. |
| first_indexed | 2024-03-09T23:22:29Z |
| format | Article |
| id | doaj.art-7318eab1ed10493bb158200486a37271 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T23:22:29Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-7318eab1ed10493bb158200486a372712023-11-23T17:24:37ZengMDPI AGJournal of Fungi2309-608X2022-05-018659010.3390/jof8060590The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in <i>Aspergillus fumigatus</i>Yong-Ho Choi0Min-Woo Lee1Kwang-Soo Shin2Department of Microbiology, Graduate School, Daejeon University, Daejeon 34520, KoreaSoonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Cheonan 31151, KoreaDepartment of Microbiology, Graduate School, Daejeon University, Daejeon 34520, KoreaHistone demethylases govern diverse cellular processes, including growth, development, and secondary metabolism. In the present study, we investigated the functions of two lysine demethylases, KdmA and KdmB, in the opportunistic human pathogenic fungus <i>Aspergillus fumigatus</i>. Experiments with mutants harboring deletions of genes encoding KdmA (Δ<i>kdmA</i>) and KdmB (Δ<i>kdmB</i>) showed that KdmA is necessary for normal growth and proper conidiation, whereas KdmB negatively regulates vegetative growth and conidiation. In both mutant strains, tolerance to H<sub>2</sub>O<sub>2</sub> was significantly decreased, and the activities of both conidia-specific catalase (CatA) and mycelia-specific catalase (Cat1) were decreased. Both mutants had significantly increased sensitivity to the guanine nucleotide synthesis inhibitor 6-azauracil (6AU). The Δ<i>kdmA</i> mutant produced more gliotoxin (GT), but the virulence was not changed significantly in immunocompromised mice. In contrast, the production of GT and virulence were markedly reduced by the loss of <i>kdmB</i>. Comparative transcriptomic analyses revealed that the expression levels of developmental process-related genes and antioxidant activity-related genes were downregulated in both mutants. Taken together, we concluded that KdmA and KdmB have opposite roles in vegetative growth, asexual sporulation, and GT production. However, the two proteins were equally important for the development of resistance to 6AU.https://www.mdpi.com/2309-608X/8/6/590<i>Aspergillus fumigatus</i>lysine demethylasetranscriptomicsoxidative stress6-azauracilgliotoxin |
| spellingShingle | Yong-Ho Choi Min-Woo Lee Kwang-Soo Shin The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in <i>Aspergillus fumigatus</i> Journal of Fungi <i>Aspergillus fumigatus</i> lysine demethylase transcriptomics oxidative stress 6-azauracil gliotoxin |
| title | The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in <i>Aspergillus fumigatus</i> |
| title_full | The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in <i>Aspergillus fumigatus</i> |
| title_fullStr | The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in <i>Aspergillus fumigatus</i> |
| title_full_unstemmed | The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in <i>Aspergillus fumigatus</i> |
| title_short | The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in <i>Aspergillus fumigatus</i> |
| title_sort | lysine demethylases kdma and kdmb differently regulate asexual development stress response and virulence in i aspergillus fumigatus i |
| topic | <i>Aspergillus fumigatus</i> lysine demethylase transcriptomics oxidative stress 6-azauracil gliotoxin |
| url | https://www.mdpi.com/2309-608X/8/6/590 |
| work_keys_str_mv | AT yonghochoi thelysinedemethylaseskdmaandkdmbdifferentlyregulateasexualdevelopmentstressresponseandvirulenceiniaspergillusfumigatusi AT minwoolee thelysinedemethylaseskdmaandkdmbdifferentlyregulateasexualdevelopmentstressresponseandvirulenceiniaspergillusfumigatusi AT kwangsooshin thelysinedemethylaseskdmaandkdmbdifferentlyregulateasexualdevelopmentstressresponseandvirulenceiniaspergillusfumigatusi AT yonghochoi lysinedemethylaseskdmaandkdmbdifferentlyregulateasexualdevelopmentstressresponseandvirulenceiniaspergillusfumigatusi AT minwoolee lysinedemethylaseskdmaandkdmbdifferentlyregulateasexualdevelopmentstressresponseandvirulenceiniaspergillusfumigatusi AT kwangsooshin lysinedemethylaseskdmaandkdmbdifferentlyregulateasexualdevelopmentstressresponseandvirulenceiniaspergillusfumigatusi |