Korotetskiy Ilya S, Shilov Sergey V, Kuznetsova Tatyana V, Zubenko Natalya, Ivanova Lyudmila, Reva Oleg N
Virology laboratory, JSC Scientific Center for Anti-Infectious Drugs, Almaty, Kazakhstan.
LLC International Engineering and Technological University, Almaty, Kazakhstan.
PLoS One. 2025 May 5;20(5):e0322006. doi: 10.1371/journal.pone.0322006. eCollection 2025.
Bacteria with similar genomes can exhibit different phenotypes due to alternative gene expression patterns. In this study, we analysed four antibiotic-resistant Staphylococcus aureus hospital isolates using transcriptomics, PacBio genome sequencing, and methylomics analyses. Transcriptomic data were obtained from cultures exposed to gentamicin, the iodine-alanine complex CC-196, and their combination. We observed strain-specific expression patterns of core and accessory genes that remained stable under antimicrobial stress - a phenomenon we term the Clonal Gene Expression Stability (CGES) that is the main discovery of the paper. An involvement of epigenetic mechanisms in stabilization of the CGES was hypothesized and statistically verified. Canonical methylation patterns controlled by type I restriction-modification systems accounted for ~ 10% of epigenetically modified adenine residues, whereas multiple non-canonically modified adenines were distributed sporadically due to imperfect DNA targeting by methyltransferases. Protein-coding sequences were characterized by a significantly lower frequency of modified nucleotides. Epigenetic modifications near transcription start codons showed a statistically significant negative association with gene expression levels. While the role of epigenetic modifications in gene regulation remains debatable, variations in non-canonical modification patterns may serve as markers of CGES.
具有相似基因组的细菌可能由于不同的基因表达模式而表现出不同的表型。在本研究中，我们使用转录组学、PacBio基因组测序和甲基化组学分析，对四株耐抗生素的医院分离金黄色葡萄球菌进行了分析。转录组数据来自暴露于庆大霉素、碘 - 丙氨酸复合物CC - 196及其组合的培养物。我们观察到核心基因和辅助基因的菌株特异性表达模式在抗菌应激下保持稳定——我们将这种现象称为克隆基因表达稳定性（CGES），这是本文的主要发现。我们假设并通过统计学验证了表观遗传机制参与了CGES的稳定。由I型限制 - 修饰系统控制的典型甲基化模式占表观遗传修饰腺嘌呤残基的约10%，而由于甲基转移酶对DNA靶向不完美，多个非典型修饰的腺嘌呤则呈散在分布。蛋白质编码序列的特征是修饰核苷酸的频率显著较低。转录起始密码子附近的表观遗传修饰与基因表达水平呈统计学上显著的负相关。虽然表观遗传修饰在基因调控中的作用仍有争议，但非典型修饰模式的变化可能作为CGES的标志物。
