Laboratory of Molecular Microbiology, Global Health Institute, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Bioinformatics Competence Center, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Nucleic Acids Res. 2023 Jun 23;51(11):5661-5677. doi: 10.1093/nar/gkad377.
Acinetobacter baumannii is a dangerous nosocomial pathogen, especially due to its ability to rapidly acquire new genetic traits, including antibiotic resistance genes (ARG). In A. baumannii, natural competence for transformation, one of the primary modes of horizontal gene transfer (HGT), is thought to contribute to ARG acquisition and has therefore been intensively studied. However, knowledge regarding the potential role of epigenetic DNA modification(s) on this process remains lacking. Here, we demonstrate that the methylome pattern of diverse A. baumannii strains differs substantially and that these epigenetic marks influence the fate of transforming DNA. Specifically, we describe a methylome-dependent phenomenon that impacts intra- and inter-species DNA exchange by the competent A. baumannii strain A118. We go on to identify and characterize an A118-specific restriction-modification (RM) system that impairs transformation when the incoming DNA lacks a specific methylation signature. Collectively, our work contributes towards a more holistic understanding of HGT in this organism and may also aid future endeavors towards tackling the spread of novel ARGs. In particular, our results suggest that DNA exchanges between bacteria that share similar epigenomes are favored and could therefore guide future research into identifying the reservoir(s) of dangerous genetic traits for this multi-drug resistant pathogen.
鲍曼不动杆菌是一种危险的医院病原体，尤其是由于其快速获得新遗传特征的能力，包括抗生素耐药基因（ARG）。在鲍曼不动杆菌中，自然转化能力，即水平基因转移（HGT）的主要模式之一，被认为有助于 ARG 的获得，因此受到了广泛研究。然而，关于表观遗传 DNA 修饰在这个过程中的潜在作用的知识仍然缺乏。在这里，我们证明了不同鲍曼不动杆菌菌株的甲基组模式存在显著差异，并且这些表观遗传标记影响转化 DNA 的命运。具体来说，我们描述了一种依赖于甲基组的现象，该现象通过有转化能力的鲍曼不动杆菌菌株 A118 影响种内和种间的 DNA 交换。我们继续鉴定和表征一种 A118 特异性的限制修饰（RM）系统，当进入的 DNA 缺乏特定的甲基化特征时，该系统会损害转化。总的来说，我们的工作有助于更全面地了解该生物体中的 HGT，并可能有助于未来解决新型 ARG 传播的问题。特别是，我们的结果表明，具有相似表观基因组的细菌之间的 DNA 交换是有利的，因此可以指导未来的研究，以确定这种多药耐药病原体的危险遗传特征的储库。
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