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，在临床中观察到了抗生素耐药性细菌速率的大量升高 设置，引起科学界和政府机构的重大关注。在 引起这些令人震惊感染的病原体是鲍曼尼杆菌，这是一种已经发展的微生物 对几乎所有可用抗生素的抗性。它的极端基因组可塑性在很大程度上由水平促进 遗传转移（HGT）过程有助于其显着的抗生素耐药表型。 转化似乎是该细菌中特别重要的HGT机制。但是， 环境信号引发了自然转化的能力，涉及的推定效应子 过程，这种现象的分子基础仍然很少了解。使用A. Baumannii A118 临床分离为模型，拟议的项目将研究人类宿主产品作为化学的作用 DNA摄取的诱导者。考虑到我们的初步数据，这表明不同的白蛋白导致 转化频率水平的显着增加，本研究将检查人血清的作用 白蛋白（HSA）和白蛋白衍生的肽在细菌能力的发展和吸收 外国DNA（目标1）。此外，我们将使用全基因组转录确定HSA的影响 A118中的分析方法（AIM 2）。通过最后一种方法，我们希望识别基因和RNA 参与自然转化的监管机构。这些知识将为分子和 细胞机制该病原体用于获得抗性基因。然后，未来的研究可以使用这些发现 开发新的方法来治疗严重的运动杆菌感染，特别是 新兴的多药抗性分离株。