The inappropriate use of antibiotics in man is driving to insurgence of pathogenic bacteria resistant to multiple drugs (MDR) representing a challenge in critical illness. The interaction of MDR bacteria with host cells can guide molecular perturbations of host transcriptional programmes involving epigenetic-sensitive mechanisms, mainly DNA methylation, histone modifications, and non-coding RNAs leading to pathogen survival. Clinical evidence of epigenetic manipulation from MDR bacteria mainly arises from Mycobacterium tuberculosis as well as Helicobacter pylori, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Legionella pneumophila infection suggesting possible biomarkers of disease. For example, DNA hypermethylation of E-cadherin (CDH1), upstream transcription factor 1/2 (USF1/2), WW domain containing oxidoreductase (WWOX), and mutL homolog 1 (MLH1) genes in gastric mucosa is correlated with malignancy suggesting useful biomarkers of early disease state. Moreover, upregulated circulating miR-361-5p, miR-889, miR-576-3p may be useful biomarkers to discriminate tuberculosis patients. Moreover, Listeria monocytogenes can indirectly induce H3 hyperacetylation leading to inflammation in human endothelial cells whereas Pseudomonas aeruginosa excretes QS 2-AA to directly induce H3 deacetylation leading to bacterial persistence in human monocytes. Remarkably, epigenetic-sensitive drugs may aid to counteract MDR in clinical setting. Trichostatin A, a histone deacetyltransferase inhibitor (HDACi), leads to AMP β-defensin 2 (HBD2) gene up-regulation in human epithelial cells suggesting a useful ‘epi-therapy’ for Escherichia coli-induced intestinal diseases. We update on the most current clinical studies focusing on epigenetic changes involved in bacterial-host interactions and their putative role as biomarkers or drug targets to improve precision medicine and personalized therapy in critical illness and transplantation setting.

人类对抗生素的不当使用导致对多种药物具有抗药性的致病细菌的激增，这代表着重大疾病的挑战。MDR细菌与宿主细胞的相互作用可以指导宿主转录程序的分子扰动，该程序涉及表观遗传敏感机制，主要是DNA甲基化，组蛋白修饰和导致病原体存活的非编码RNA。MDR细菌的表观遗传操作的临床证据主要来自结核分枝杆菌，幽门螺杆菌，大肠杆菌，单核细胞增生李斯特菌，铜绿假单胞菌和肺炎军团菌感染，提示可能是疾病的生物标志物。例如，E-cadherin（CDH1），上游转录因子1/2（USF1 / 2），含WW结构域的氧化还原酶（WWOX）和mutL同源1（MLH1）基因与胃黏膜恶性程度相关，表明早期疾病状态有用的生物标志物。此外，上调的循环miR-​​361-5p，miR-889，miR-576-3p可能是区分结核病患者的有用生物标志物。此外，单核细胞增生性李斯特菌可间接诱导H3超乙酰化，导致人内皮细胞发炎，而铜绿假单胞菌排泄QS 2-AA以直接诱导H3脱乙酰化，导致细菌在人类单核细胞中持续存在。值得注意的是，对表观遗传敏感的药物可能有助于在临床上抵消MDR。组蛋白脱乙酰基转移酶抑制剂（HDACi）曲古他汀A导致人上皮细胞中的AMPβ-防御素2（HBD2）基因上调，表明对大肠杆菌诱导的肠道疾病是一种有用的“表皮疗法” 。我们更新了最新的临床研究，重点关注细菌-宿主相互作用中涉及的表观遗传学变化及其作为生物标志物或药物靶标的推定作用，以改善重大疾病和移植环境中的精准医学和个性化治疗。