Laboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of Korea.
Department of Microbiology and Immunology, Department of Biomedical Science, and Cancer Research Institute, College of Medicine, Seoul National University, Jongno-gu, Seoul, Republic of Korea.
Commun Biol. 2024 Oct 5;7(1):1274. doi: 10.1038/s42003-024-06978-w.
This study uncovers the molecular processes governing the adaptive evolution of multidrug-resistant (MDR) pathogens without antibiotic pressure. Genomic analysis of MDR Acinetobacter baumannii cells cultured for 8000 generations under starvation conditions (EAB1) or nutrient-rich conditions (EAB2) revealed significant genomic changes, primarily by insertion sequence (IS)-mediated insertions and deletions. Only two Acinetobacter-specific prophage-related deletions and translocations were observed in the EAB1 strain. Both evolved strains exhibited higher virulence in mouse infection studies, each with different modes of action. The EAB1 strain displayed a heightened ability to cross the epithelial barrier of human lung tissue, evade the immune system, and spread to lung tissues, ultimately resulting in cellular mortality. In contrast, the EAB2 strain strongly attached to epithelial cells, leading to increased synthesis of proinflammatory cytokines and chemokines. The genomic alterations and increased virulence observed in evolved strains during short-term evolution underscore the need for caution when handling these pathogens, as these risks persist even without antibiotic exposure.
这项研究揭示了在没有抗生素压力的情况下，多药耐药（MDR）病原体适应性进化的分子过程。对饥饿条件下（EAB1）或营养丰富条件下（EAB2）培养 8000 代的多药耐药鲍曼不动杆菌（Acinetobacter baumannii）细胞进行基因组分析，揭示了显著的基因组变化，主要是通过插入序列（IS）介导的插入和缺失。在 EAB1 菌株中仅观察到两个与 Acinetobacter 特异性噬菌体相关的缺失和易位。在小鼠感染研究中，两种进化后的菌株均表现出更高的毒力，每种菌株都有不同的作用模式。EAB1 菌株表现出更高的穿过人肺组织上皮屏障、逃避免疫系统和扩散到肺组织的能力，最终导致细胞死亡。相比之下，EAB2 菌株强烈附着在上皮细胞上，导致促炎细胞因子和趋化因子的合成增加。在短期进化过程中，进化菌株中观察到的基因组改变和毒力增加，强调了在处理这些病原体时需要谨慎，因为即使没有抗生素暴露，这些风险仍然存在。
