Alkasir Rashad, Ma Yanan, Liu Fei, Li Jing, Lv Na, Xue Yong, Hu Yongfei, Zhu Baoli
1 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology , Chinese Academy of Sciences, Beijing, China .
2 Beijing Key Laboratory of Microbial Drug Resistance and Resistome , Beijing, China .
Microb Drug Resist. 2018 Dec;24(10):1466-1474. doi: 10.1089/mdr.2017.0341. Epub 2018 Jun 14.
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.
鲍曼不动杆菌是一种非发酵革兰氏阴性杆菌。鲍曼不动杆菌的耐药性是临床感染治疗的一个重大障碍。持留菌的存在可能是治疗失败和复发的原因，并且这类细菌可能是耐药率上升的驱动力。在本研究中，以鲍曼不动杆菌ATCC 19606为对象来探究鲍曼不动杆菌持留菌的基本特征。用最低抑菌浓度50倍的抗生素处理鲍曼不动杆菌培养物，导致存活的耐药物持留菌出现明显的平稳期。用头孢他啶裂解敏感菌，分离出非复制菌用于RNA测序的转录组分析。我们分析了鲍曼不动杆菌持留菌的转录组，鉴定出显著差异表达的基因及其富集的通路。结果显示，在持留菌培养期间，GP49（HigB）/Cro（HigA）和DUF1044/RelB毒素/抗毒素系统均显著增加。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）的活性在抗生素处理后急剧下降，并在持留菌阶段保持较低水平，而芳香族化合物降解基因仅在持留菌中上调。这些结果表明芳香族化合物降解基因参与了持留菌的形成和维持。它们进一步首次深入了解了鲍曼不动杆菌中持留菌形成的机制。
