Identifying host human products responsible for natural transformation of resistance traits in Acinetobacter baumannii

鉴定负责鲍曼不动杆菌抗性特征自然转化的宿主人类产物

• 批准号: 10093070
• 负责人: Maria Soledad Ramirez
• 金额: $ 10.65万
• 依托单位: CALIFORNIA STATE UNIVERSITY FULLERTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-07 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10093070
• 关键词: Acinetobacter; Acinetobacter Infections; Acinetobacter baumannii; Albumins; Amino Acid Motifs; Amino Acid Sequence; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Antibiotic Resistance; Bacterial Genes; Biological Assay; Blood; Candidate Disease Gene; Caseins; Chemicals; Clinical; Code; Communities; Competence; DNA; Data; Development; ESKAPE pathogens; Frequencies; Future; Gene Expression Profiling; Gene Transfer; Genes; Genetic; Genetic Materials; Genetic Models; Genome; Goals; Government Agencies; Health; Human; Infection; Knowledge; Legionella pneumophila; Medical; Modeling; Molecular; Multi-Drug Resistance; Multidrug-resistant Acinetobacter; Mutation; Nosocomial Infections; Peptides; Phenotype; Play; Process; Proteins; RNA; Regulatory Element; Research; Resistance; Resistance development; Role; Scientist; Serum Albumin; Signal Transduction; Source; Streptococcus; Structure; System; Testing; Therapeutic; Vibrio cholerae; antimicrobial; bacterial resistance; enhancing factor; genetic resistance; insight; member; microorganism; novel strategies; pathogen; pathogenic bacteria; resistance gene; tool; trait; transmission process; uptake; whole genome

PROJECT SUMMARY In recent years, a massive increase in the rates of antibiotic resistant bacteria has been observed in clinical settings, causing significant concern from both the scientific community and government agencies. Among the pathogens causing these alarming infections is Acinetobacter baumannii, a microorganism that has developed resistance to almost all available antibiotics. Its extreme genome plasticity, largely facilitated by horizontal genetic transfer (HGT) processes, has contributed to its remarkable antibiotic-resistance phenotype. Transformation seems to be a particularly important HGT mechanism in this bacterium. However, the environmental signals triggering competence for natural transformation, the putative effectors involved in this process, and the molecular basis of this phenomenon are still poorly understood. Using the A. baumannii A118 clinical isolate as a model, the proposed project will examine the role of human host products as chemical inducers of DNA uptake. Considering our preliminary data, which show that different albumins cause a significant increase in the level of transformation frequency, this study will examine the role of Human Serum Albumin (HSA) and albumin-derived peptides in the development of bacterial competence and the uptake of foreign DNA (Aim 1). Moreover, we will determine the effects of HSA using a whole-genome transcriptional profiling approach in A118 (Aim 2). Through this last approach, we expect to identify genes and RNA regulators involved in natural transformation. This knowledge will provide critical insights into the molecular and cellular mechanism this pathogen uses to acquire resistance genes. Future studies can then use these findings to develop novel approaches to treat severe Acinetobacter human infections, particularly those caused by emerging multidrug-resistant isolates.

项目摘要 近年来，在临床中观察到抗生素耐药菌的比率大幅增加， 这引起了科学界和政府机构的严重关注。中 引起这些令人担忧的感染的病原体是鲍氏不动杆菌， 对几乎所有可用的抗生素都有耐药性。其极端的基因组可塑性，在很大程度上促进了水平 遗传转移（HGT）过程，有助于其显着的抗虫表型。 转化似乎是这种细菌中特别重要的HGT机制。但 环境信号触发自然转化的能力，参与这一过程的假定效应子， 这一过程，以及这种现象的分子基础仍然知之甚少。利用A.鲍曼不动杆菌A118 作为一个模型，拟议的项目将研究人类宿主产品作为化学品的作用， DNA摄取的诱导剂。考虑到我们的初步数据，这些数据表明不同的白蛋白会导致 显着增加的转化频率的水平，这项研究将检查的作用，人血清 白蛋白（HSA）和白蛋白衍生肽在细菌感受态的发展和 外源DNA（Aim 1）。此外，我们将使用全基因组转录检测来确定HSA的作用。 A118（目标2）中的分析方法。通过这最后一种方法，我们希望能够识别基因和RNA， 参与自然转化的调节器。这些知识将提供关键的见解，分子和 这种病原体用来获得抗性基因的细胞机制。未来的研究可以利用这些发现 开发新的方法来治疗严重的人类不动杆菌感染，特别是由以下原因引起的感染： 新出现的多重耐药菌株。