Microfluidic platform for stress-induced rapid antibiotic susceptibility testing

用于应激诱导快速抗生素敏感性测试的微流控平台

• 批准号: 8839194
• 负责人: Alexis F Sauer-Budge
• 金额: $ 39.4万
• 依托单位: FRAUNHOFER CENTER /MANUFACTURING INNOV
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-17 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8839194
• 关键词: Address; Aminoglycosides; Anabolism; Antibiotic Resistance; Antibiotic Therapy; Antibiotic susceptibility; Antibiotics; Bacteria; Bacterial Infections; Biochemical Pathway; Biological Assay; Biological Models; Cell Death; Cell Wall; Cell physiology; Cells; Ciprofloxacin; Clindamycin; Clinical; Clinical Microbiology; Combined Antibiotics; Communicable Diseases; Complement; Consult; DNA; Daptomycin; Data; Diagnostic; Diagnostic Procedure; Disease; Drug resistance; Effectiveness; Enzymes; Epidemiologic Studies; Erythromycin; Evaluation; Funding; Generations; Genetic Transcription; Genetic screening method; Goals; Government; Gram-Negative Bacteria; Gram-Positive Bacteria; Growth; Health; High Prevalence; Ionic Strengths; Laboratories; Lead; Literature; Mechanical Stress; Mechanics; Metabolism; Methicillin; Methicillin Resistance; Methodology; Methods; Microbe; Microfluidics; Minimum Inhibitory Concentration measurement; Molecular; Monitor; Multi-Drug Resistance; Organism; Oxidative Stress; Pathway interactions; Patient Noncompliance; Patients; Pattern; Performance; Persons; Pharmacotherapy; Physicians; Predisposition; Prevalence; Process; Proliferating; Protein Biosynthesis; Public Health; Publishing; Reagent; Regimen; Reporter; Research; Resistance; Sampling; Scientist; Specificity; Specimen; Staphylococcus aureus; Stress; Sulfonamides; System; Techniques; Technology; Testing; Tetracyclines; Time; Vancomycin; Work; bacterial resistance; bactericide; base; beta-Lactams; biological adaptation to stress; clinical practice; combat; cost; drug candidate; field study; improved; innovation; killings; new technology; novel; novel diagnostics; pathogen; rapid detection; rapid technique; repaired; research study; resistance mechanism; resistant strain; response; screening; shear stress; skills; stressor; success; tool; trend

DESCRIPTION (provided by applicant): Current standard methods for detecting antibiotic susceptibility are based on the ability of the bacteria to proliferate in the presence of antibiotis, and thus these techniques are time-consuming, costly, and insensitive, particularly for evaluation of slow-growing organisms. To develop a truly rapid susceptibility test, one must circumvent the need for growth. We are developing a microfluidic test that interrogates the response of cells to antibiotics in the presence of mechanical and/or soluble stressors and thereby minimizes the time to results. The core of the hypothesis is that by straining the cell, we induce the cellular repair processes and associated biochemical pathways. These pathways are often targets of antibiotics (e.g., cell wall biosynthesis, protein synthesis, DNA transcription). f the antibiotic hinders those repair processes, the cell will die under the continued application of stress. We posit that monitoring cell death under stress in the presence of antibiotics can provide phenotypic information in an ultra-rapid time frame allowing physicians to make appropriate antibiotic treatment choices sooner. We envisage that this methodology would complement the existing rapid tests based on molecular diagnostics (e.g., PCR) because it would provide a low-cost rapid method that delivers phenotypic information. While genetic tests provide precise information for epidemiological studies, the high reagent costs, relatively high operator skills required, and limited clinical utility continue to limit widespread routine use. Furthermore, the molecular diagnostics suffer from a high number of false positives and unacceptable performance in non-sterile specimens (e.g., polymicrobial samples). As our method could be automated and is based on phenotypic changes, we believe it is superior as a routine clinical diagnostic providing physicians with the information they need to treat their patients, namely what antibiotic to use to kill the infecting pathogen. The method can be multiplexed (multiple antibiotics and multiple organisms) and can be integrated with current bacterial identification methodologies, thus it has the potential to be the basis of a new diagnostics system that rapidly provides clinicians with both identification and antibiotic susceptibility profiles in a timeframe that is much shorter than is currently possible. The method also opens new avenues of research into how stress can potentiate the effects of antibiotics. Once developed, the technique could also be used as a rapid screening technology for new antibiotic drug candidates.

描述（由申请人提供）：目前检测抗生素敏感性的标准方法是基于细菌在抗生素存在下增殖的能力，因此这些技术耗时，昂贵且不敏感，特别是对于缓慢生长的生物体的评估。要开发一种真正快速的敏感性测试，就必须避开对生长的需求。我们正在开发一种微流体测试，可以在机械和/或可溶性压力源存在的情况下询问细胞对抗生素的反应，从而最大限度地缩短获得结果的时间。这个假说的核心是，通过使细胞紧张，我们