AB5075, a Highly Virulent Isolate of Acinetobacter baumannii, as a Model Strain for the Evaluation of Pathogenesis and Antimicrobial Treatments.
AB5075, a Highly Virulent Isolate of Acinetobacter baumannii, as a Model Strain for the Evaluation of Pathogenesis and Antimicrobial Treatments.
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DOI：
10.1128/mbio.01076-14
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发表时间：
2014-05-27
期刊：
影响因子：
6.4
通讯作者：
Zurawski DV
中科院分区：
文献类型：
--
作者：
Jacobs AC;Thompson MG;Black CC;Kessler JL;Clark LP;McQueary CN;Gancz HY;Corey BW;Moon JK;Si Y;Owen MT;Hallock JD;Kwak YI;Summers A;Li CZ;Rasko DA;Penwell WF;Honnold CL;Wise MC;Waterman PE;Lesho EP;Stewart RL;Actis LA;Palys TJ;Craft DW;Zurawski DV
鲍曼不动杆菌被认为是一种新兴的细菌病原体，因为它具有在干燥状态下存活时间长、有效的医院传播和获得抗生素耐药基因的固有能力等特征。鲍曼不动杆菌研究领域的一个迫切需要是一种合适的模型菌株，它能代表目前的临床分离株，在已建立的动物模型中具有高毒力，并且可以进行基因操纵。为了确定合适的菌株，对最近美国军事临床分离的一组遗传多样性进行了评估。采用脉冲场凝胶电泳和多重PCR对33株鲍曼不动杆菌进行了遗传多样性分析。随后，在小鼠肺部和mellonia感染模型中测试了5个有代表性的分离株。在两种动物模型中，一种菌株AB5075的感染比其他菌株的感染严重得多，因为存活率显著降低。AB5075在大鼠开放性骨折模型中也引起骨髓炎，而另一株没有。此外，在AB5075中成功生成了Tn5转座子文库，并完成了外源基因通过Tn7插入AB5075染色体的过程，这表明该分离物在遗传上可用于研究目的。最后，抗生素利福平的概念验证实验表明，该菌株可用于动物模型，以评估多种参数下的治疗方法，包括存活率和肺部细菌负荷。我们认为AB5075可以作为鲍曼不动杆菌的模型菌株，因为它的分离时间较晚，具有多药耐药性，在动物模型中具有可复制的毒力，并且具有遗传易感性。鲍曼不动杆菌感染的发病率在过去十年中有所增加，不幸的是，这种细菌的抗生素耐药性也有所增加。鲍曼不动杆菌现在占美国所有医院获得性感染的10%以上，在败血症和肺炎患者中有50%的死亡率。大多数关于鲍曼不动杆菌致病性的研究都集中在不能真正代表目前从患者身上分离出的多重耐药菌株的分离株上。在对一组不同的体外和体内实验分离株进行筛选后，由于菌株AB5075具有抗生素耐药性，并且在动物模型中具有更高的毒力，因此更适合进行研究。此外，AB5075对四环素和潮霉素敏感，这使得它易于基因操作。综上所述，这些特性使AB5075成为研究该物种毒力和致病性以及测试新型抗菌素的良好候选者。
Acinetobacter baumannii is recognized as an emerging bacterial pathogen because of traits such as prolonged survival in a desiccated state, effective nosocomial transmission, and an inherent ability to acquire antibiotic resistance genes. A pressing need in the field of A. baumannii research is a suitable model strain that is representative of current clinical isolates, is highly virulent in established animal models, and can be genetically manipulated. To identify a suitable strain, a genetically diverse set of recent U.S. military clinical isolates was assessed. Pulsed-field gel electrophoresis and multiplex PCR determined the genetic diversity of 33 A. baumannii isolates. Subsequently, five representative isolates were tested in murine pulmonary and Galleria mellonella models of infection. Infections with one strain, AB5075, were considerably more severe in both animal models than those with other isolates, as there was a significant decrease in survival rates. AB5075 also caused osteomyelitis in a rat open fracture model, while another isolate did not. Additionally, a Tn5 transposon library was successfully generated in AB5075, and the insertion of exogenous genes into the AB5075 chromosome via Tn7 was completed, suggesting that this isolate may be genetically amenable for research purposes. Finally, proof-of-concept experiments with the antibiotic rifampin showed that this strain can be used in animal models to assess therapies under numerous parameters, including survival rates and lung bacterial burden. We propose that AB5075 can serve as a model strain for A. baumannii pathogenesis due to its relatively recent isolation, multidrug resistance, reproducible virulence in animal models, and genetic tractability. The incidence of A. baumannii infections has increased over the last decade, and unfortunately, so has antibiotic resistance in this bacterial species. A. baumannii is now responsible for more than 10% of all hospital-acquired infections in the United States and has a >50% mortality rate in patients with sepsis and pneumonia. Most research on the pathogenicity of A. baumannii focused on isolates that are not truly representative of current multidrug-resistant strains isolated from patients. After screening of a panel of isolates in different in vitro and in vivo assays, the strain AB5075 was selected as more suitable for research because of its antibiotic resistance profile and increased virulence in animal models. Moreover, AB5075 is susceptible to tetracycline and hygromycin, which makes it amenable to genetic manipulation. Taken together, these traits make AB5075 a good candidate for use in studying virulence and pathogenicity of this species and testing novel antimicrobials.