Identification of a <i>Neisseria gonorrhoeae</i> Histone Deacetylase: Epigenetic Impact on Host Gene Expression
Epigenetic reprogramming in macrophages is termed trained innate immunity, which regulates immune tolerance and limits tissue damage during infection. <i>Neisseria gonorrhoeae</i> is a strict human pathogen that causes the sexually transmitted infection termed gonorrhea. Here, we report...
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| Format: | Article |
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MDPI AG
2020-02-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/9/2/132 |
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| author | Susu M. Zughaier Corinne E. Rouquette-Loughlin William M. Shafer |
| author_facet | Susu M. Zughaier Corinne E. Rouquette-Loughlin William M. Shafer |
| author_sort | Susu M. Zughaier |
| collection | DOAJ |
| description | Epigenetic reprogramming in macrophages is termed trained innate immunity, which regulates immune tolerance and limits tissue damage during infection. <i>Neisseria gonorrhoeae</i> is a strict human pathogen that causes the sexually transmitted infection termed gonorrhea. Here, we report that this pathogen harbors a gene that encodes a histone deacetylase-like enzyme (Gc-HDAC) that shares high 3D-homology to human HDAC1, HDAC2 and HDAC8. A Gc-HDAC null mutant was constructed to determine the biologic significance of this gene. The results showed that WT gonococci reduced the expression of host defense peptides LL-37, HBD-1 and SLPI in macrophages when compared to its Gc-HDAC-deficient isogenic strain. The enrichment of epigenetic marks in histone tails control gene expression and are known to change during bacterial infections. To investigate whether gonococci exert epigenetic modifications on host chromatin, the enrichment of acetylated lysine 9 in histone 3 (H3K9ac) was investigated using the TLR-focused ChIP array system. The data showed that infection with WT gonococci led to higher H3K9ac enrichment at the promoters of pro-inflammatory mediators’ genes, many TLRs, adaptor proteins and transcription factors, suggesting gene activation when compared to infection with the Gc-HDAC-deficient mutant. Taken together, the data suggest that gonococci can exert epigenetic modifications on host cells to modulate certain macrophage defense genes, leading to a maladaptive state of trained immunity. |
| first_indexed | 2024-04-13T09:08:34Z |
| format | Article |
| id | doaj.art-210cdff4e4874bd0934963b2e842e226 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-04-13T09:08:34Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-210cdff4e4874bd0934963b2e842e2262022-12-22T02:52:55ZengMDPI AGPathogens2076-08172020-02-019213210.3390/pathogens9020132pathogens9020132Identification of a <i>Neisseria gonorrhoeae</i> Histone Deacetylase: Epigenetic Impact on Host Gene ExpressionSusu M. Zughaier0Corinne E. Rouquette-Loughlin1William M. Shafer2Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, P.O. Box 2713, Doha, QatarLaboratory of Bacterial Pathogenesis, Department of Veterans Affairs Medical Center, Decatur, GA 30033, USALaboratory of Bacterial Pathogenesis, Department of Veterans Affairs Medical Center, Decatur, GA 30033, USAEpigenetic reprogramming in macrophages is termed trained innate immunity, which regulates immune tolerance and limits tissue damage during infection. <i>Neisseria gonorrhoeae</i> is a strict human pathogen that causes the sexually transmitted infection termed gonorrhea. Here, we report that this pathogen harbors a gene that encodes a histone deacetylase-like enzyme (Gc-HDAC) that shares high 3D-homology to human HDAC1, HDAC2 and HDAC8. A Gc-HDAC null mutant was constructed to determine the biologic significance of this gene. The results showed that WT gonococci reduced the expression of host defense peptides LL-37, HBD-1 and SLPI in macrophages when compared to its Gc-HDAC-deficient isogenic strain. The enrichment of epigenetic marks in histone tails control gene expression and are known to change during bacterial infections. To investigate whether gonococci exert epigenetic modifications on host chromatin, the enrichment of acetylated lysine 9 in histone 3 (H3K9ac) was investigated using the TLR-focused ChIP array system. The data showed that infection with WT gonococci led to higher H3K9ac enrichment at the promoters of pro-inflammatory mediators’ genes, many TLRs, adaptor proteins and transcription factors, suggesting gene activation when compared to infection with the Gc-HDAC-deficient mutant. Taken together, the data suggest that gonococci can exert epigenetic modifications on host cells to modulate certain macrophage defense genes, leading to a maladaptive state of trained immunity.https://www.mdpi.com/2076-0817/9/2/132<i>neisseria gonorrhoeae</i>hdacinfectionepigenetich3k9acmacrophagesurvivalcytokineschemokinesgonorrhea |
| spellingShingle | Susu M. Zughaier Corinne E. Rouquette-Loughlin William M. Shafer Identification of a <i>Neisseria gonorrhoeae</i> Histone Deacetylase: Epigenetic Impact on Host Gene Expression Pathogens <i>neisseria gonorrhoeae</i> hdac infection epigenetic h3k9ac macrophage survival cytokines chemokines gonorrhea |
| title | Identification of a <i>Neisseria gonorrhoeae</i> Histone Deacetylase: Epigenetic Impact on Host Gene Expression |
| title_full | Identification of a <i>Neisseria gonorrhoeae</i> Histone Deacetylase: Epigenetic Impact on Host Gene Expression |
| title_fullStr | Identification of a <i>Neisseria gonorrhoeae</i> Histone Deacetylase: Epigenetic Impact on Host Gene Expression |
| title_full_unstemmed | Identification of a <i>Neisseria gonorrhoeae</i> Histone Deacetylase: Epigenetic Impact on Host Gene Expression |
| title_short | Identification of a <i>Neisseria gonorrhoeae</i> Histone Deacetylase: Epigenetic Impact on Host Gene Expression |
| title_sort | identification of a i neisseria gonorrhoeae i histone deacetylase epigenetic impact on host gene expression |
| topic | <i>neisseria gonorrhoeae</i> hdac infection epigenetic h3k9ac macrophage survival cytokines chemokines gonorrhea |
| url | https://www.mdpi.com/2076-0817/9/2/132 |
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