Characterization and Transcriptome Analysis of Acinetobacter baumannii Persister Cells
Characterization and Transcriptome Analysis of Acinetobacter baumannii Persister Cells
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鲍曼不动杆菌持久细胞的表征和转录组分析
DOI：
10.1089/mdr.2017.0341
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发表时间：
2018-06-14
影响因子：
2.6
通讯作者：
Zhu, Baoli
中科院分区：
文献类型：
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作者：
Alkasir, Rashad;Ma, Yanan;Zhu, Baoli
鲍曼不动杆菌是一种非发酵革兰氏阴性杆菌。A.鲍曼不动杆菌耐药性是临床感染治疗的一个重要障碍。持久细胞（persisters）的存在可能是治疗失败和复发的原因，这些细胞可能是耐药率上升的驱动力。在本研究中，A.以鲍曼不动杆菌ATCC 19606为靶标，探索了鲍曼不动杆菌的基本特征。鲍曼不动杆菌抗生素治疗A.在50倍最小抑制浓度下的鲍曼不动杆菌培养物导致存活的耐药持留菌的明显平台。用头孢他啶裂解敏感细菌，分离非复制细菌，使用RNA测序进行转录组分析。我们分析了A.鲍曼不动杆菌持续存在，并确定了显着差异表达的基因，以及他们丰富的途径。结果表明，GP 49（HigB）/Cro（HigA）和DUF 1044/RelB毒素/抗毒素系统在持续潜伏期均显著增加。此外，某些代谢途径（如电子传递，三磷酸腺苷[ATP]和柠檬酸循环）的活动在抗生素治疗后急剧下降，并在持续期内保持较低水平，而芳香族化合物降解基因仅在持续期内上调。这些结果表明芳香族化合物降解基因参与了持久性的形成和维持。这些结果进一步揭示了A.鲍曼不动杆菌。
Acinetobacter baumannii is a nonfermenting Gram-negative bacillus. A. baumannii resistance is a significant obstacle to clinical infection treatment. The existence of persister cells (persisters) might represent the reason for therapy failure and relapse, and such cells may be the driving force behind rising resistance rates. In this study, A. baumannii ATCC 19606 was used as a target to explore the essential features of A. baumannii persisters. Antibiotic treatment of A. baumannii cultures at 50-fold the minimum inhibitory concentration resulted in a distinct plateau of surviving drug-tolerant persisters. The sensitive bacteria were lysed with ceftazidime, and the nonreplicating bacteria were isolated for transcriptome analysis using RNA sequencing. We analyzed the transcriptome of A. baumannii persisters and identified significantly differentially expressed genes, as well as their enriched pathways. The results showed that both the GP49 (HigB)/Cro (HigA) and DUF1044/RelB toxin/antitoxin systems were significantly increased during the persister incubation period. In addition, the activities of certain metabolic pathways (such as electron transport, adenosine triphosphate [ATP], and the citrate cycle) decreased sharply after antibiotic treatment and remained low during the persister period, while aromatic compound degradation genes were only upregulated in persisters. These results suggest the involvement of aromatic compound degradation genes in persister formation and maintenance. They further provide the first insight into the mechanism of persister formation in A. baumannii.