An increasing number of studies have reported that bacterial DNA methylation has important functions beyond the roles in restriction-modification systems, including the ability of affecting clinically relevant phenotypes such as virulence, host colonization, sporulation, biofilm formation, among others. Although insightful, such studies have a largely ad hoc nature and would benefit from a systematic strategy enabling a joint functional characterization of bacterial methylomes by the microbiology community. In this opinion article, we propose that highly conserved DNA methyltransferases (MTases) represent a unique opportunity for bacterial epigenomic studies. These MTases are rather common in bacteria, span various taxonomic scales, and are present in multiple human pathogens. Apart from well-characterized core DNA MTases, like those from Vibrio cholerae, Salmonella enterica, Clostridioides difficile, or Streptococcus pyogenes, multiple highly conserved DNA MTases are also found in numerous human pathogens, including those belonging to the genera Burkholderia and Acinetobacter. We discuss why and how these MTases can be prioritized to enable a community-wide, integrative approach for functional epigenomic studies. Ultimately, we discuss how some highly conserved DNA MTases may emerge as promising targets for the development of novel epigenetic inhibitors for biomedical applications.

越来越多的研究报告称，细菌 DNA 甲基化除了在限制修饰系统中的作用之外，还具有重要的功能，包括影响临床相关表型的能力，如毒力、宿主定植、孢子形成、生物膜形成等。尽管有见地，但此类研究在很大程度上是临时性的自然，并将受益于系统策略，使微生物学界能够对细菌甲基化组进行联合功能表征。在这篇意见文章中，我们提出高度保守的 DNA 甲基转移酶 (MTases) 代表了细菌表观基因组研究的独特机会。这些 MTases 在细菌中相当常见，跨越各种分类尺度，并且存在于多种人类病原体中。除了充分表征的核心 DNA MTases，如来自霍乱弧菌、肠沙门氏菌、艰难梭菌或化脓性链球菌的那些，在许多人类病原体中也发现了多种高度保守的 DNA MTases，包括那些属于伯克霍尔德氏菌属的病原体和不动杆菌。我们讨论了为什么以及如何优先考虑这些 MTase，以便为功能性表观基因组研究提供社区范围的综合方法。最后，我们讨论了一些高度保守的 DNA MTase 如何成为开发用于生物医学应用的新型表观遗传抑制剂的有希望的目标。