Table 1.

Some clinical evidence on the role of epigenetic-sensitive mechanisms in bacterial-host interactions.

Bacterial infection	Interacting host cells	Epigenetic change	Targeted genes and signalling pathways	Putative clinical role	Refs
DNA methylation
H. pilori	Epithelial cells of gastric mucosa	DNA hypermethylation	Down-regulation of CDH1, USF1/2, WWOX, MLH1, and miRNA genes Up-regulation of oncogenic pathways	Diagnostic biomarkers of early gastric carcinogenesis	[23–27]
UPEC	Uroepithelial cells	DNA hypermethylation	Down-regulation of CDKN2A gene Blocking of cell proliferation check point	Diagnostic biomarkers of urinary tract infections	[28]
M. tuberculosis	Monocyte-derived DCs	DNA hypomethylation in non canonical sites; Gain of histone activation marks (H3K27ac)	Up-regulation of thousands of genes encoding for TFs, such as NFKB1 and IRF4 Regulation of pathways involved in transcription, signalling, apoptosis, B and T cell activation	Molecular mechanisms of ‘trained immunity’	[29]
	Macrophages	DNA hypermethylation	Deregulation of HLA, IL16, IL17, CCL17, CCL18, and some non-coding RNA genes Modulation of immune response, chromatin reorganization, DNA replication and repair pathways	Non-canonical bacterial epigenetic strategies might be innovative drug targets	[30]
Histone modifications
L. monocytogenes	Human umbilical venous endothelial cells	Increased acetylation of H4 and phosphorylation/acetylation of H3	Overexpression of IL-8 gene Increased inflammation by chemokine secretion and NF-KB activation	Biomarkers and drug targets	[38]
P. aeruginosa	Monocytes	Global deacetylation of H3K18	Downregulation of TNF, IL-1B, and MCP-1 genes Reduced inflammation and induction of tolerance	Biomarkers and drug targets	[39]
L. pneumophila	Human monocyte/ alveolar epithelial cell lines (A549)	Promoter genes	Repression of TLR5 and IL6 genes Promotion of bacterial replication	Biomarkers and drug targets	[42]
MiRNAs
M. tuberculosis	Plasma	Differentially expressed circulating miRNAs	Upregulation of miR-361-5p, miR-889, and miR-576-3p in patients vs controls Boinformatic prediction of targeted genes involved in immune system development (e.g., SP-1)	Biomarkers of early detection of infection	[43]
	Plasma	Differentially expressed circulating miRNAs	Downregulation of miR-769-5p, miR-320a, and miR-22-3p Downregulation of miR-320a levels in “non-responder“ patients vs controls	Biomarkers for active infection Biomarker of drug-resistant patients	[44]
	Plasma	Differentially expressed circulating miRNAs	Upregulation of miR-484, miR-425, and miR-96 in patients vs controls Bioinformatic prediction of targeted genes involved in regulation of the immune system and other pathways	Biomarkers of active infection	[45]
LPS	Human cultured skin fibroblasts	Differentially expressed cellular miRNAs	Downregulation of miR-211-3p after treatment with LPS vs not treated cells Endoplasmic reticulum stress	Putative useful epi-therapy for wound healing	[46]
LncRNAs
M. tuberculosis	Peripheral blood mononuclear cells	//	Upregulation of CTD-2331D11.3 and AC079779.5 lncRNA genes Bioinformatic prediction of NK-cytotoxicity, antigen processing and presentation deregulated pathways	Biomarkers of resistant infection	[47]

Abbreviations: CCL17: chemokine (C-C motif) ligand 17; CCL18: chemokine (C-C motif) ligand 18; DCs: dendritic cells; H3K14: histone 3 lysine 14; HLA: human leukocyte antigen; IL-1: interleukin 1; IL-6: interleukin 6; IL-16: interleukin 16; IL17: interleukin 17; IL-1β: interleukin-1 β; IRF4: interferon regulatory factor 4; Lnc-RNA: long non-coding RNAs; LPS: lipopolysaccharides; MCP-1: monocyte chemoattractant protein-1; miRNA: microRNAs; ncRNA: non-coding RNA; NFKB1: nuclear factor kappa B subunit 1; NK: natural killer; NFKB: nuclear factor kappa B; SCFA: short chain fatty acids; Sirt2: NAD-dependent deacetylase sirtuin 2; SP1: SP1 transcription factor; TLR5: toll-like receptor 5; TF: transcription factor; UPEC: uropathogenic Escherichia coli; TNF: tumour necrosis factor.