Identification of a neisseria gonorrhoeae histone deacetylase: Epigenetic impact on host gene expression

• Type of Material: Article
• Authors: Susu Zughaier, Emory University; Corinne Loughlin, Emory University; William Shafer, Emory University
• Language: English
• Date: 2020-02-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/pathogens9020132
• Title of Journal or Parent Work: Pathogens
• Volume: 9
• Issue: 2
• Grant/Funding Information: W.M.S. was supported by a Senior Research Career Award from the Biomedical Laboratory Research and Development Service of the Department of Veterans Affairs.; This research was funded by a Development Research Program grant to S.M.Z. from the Henry M. Jackson Foundation through an NIH grant 1U19AI113170-01 (Ann E. Jerse, PI, Uniformed Services University, Bethesda, MD, USA) and a VA Merit Award grant (510 1BX000112-07) to W.M.S. from the Biomedical Laboratory Research and Development Service of the Department of Veterans Affairs.
• Keywords: H3K9ac; chemokines; survival; gonorrhea; epigenetic; macrophage; HDAC; infection; Neisseria gonorrhoeae; cytokines
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Immunology; Biology, Microbiology

Abstract

Epigenetic reprogramming in macrophages is termed trained innate immunity, which regulates immune tolerance and limits tissue damage during infection. Neisseria gonorrhoeae 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.