Novel Methodology for Rapid Antibiotic Susceptibiility Testing in S. aureus

金黄色葡萄球菌快速抗生素敏感性测试的新方法

• 批准号: 7660965
• 负责人: Alexis F Sauer-Budge
• 金额: $ 20.13万
• 依托单位: FRAUNHOFER CENTER /MANUFACTURING INNOV
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-23 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7660965
• 关键词: Address; Anabolism; Antibiotic Resistance; Antibiotic Therapy; Antibiotic susceptibility; Antibiotics; Bacteria; Bacterial Antibiotic Resistance; Bacterial Infections; Biological Models; Boston; Cell Wall; Cell membrane; Cells; Chemicals; Clinical; Community Healthcare; Community-Acquired Infections; Culture Media; Detection; Development; Diagnostic; Diagnostic Procedure; Disease; Drug resistance; Fluorescence Microscopy; Fluorescent Dyes; Growth; Hospitals; Infection; Liquid substance; Literature; Mechanical Stress; Membrane Potentials; Methicillin; Methicillin Resistance; Methodology; Methods; Microbe; Modality; Monitor; Monobactams; Multi-Drug Resistance; Nature; Nosocomial Infections; Optics; Organism; Pathway interactions; Patient Noncompliance; Pharmaceutical Preparations; Pharmacotherapy; Phase; Photography; Physicians; Predisposition; Prevalence; Protein Synthesis Inhibitors; Protocols documentation; Public Health; Resistance; Risk Factors; Role; Specificity; Staging; Staining method; Stains; Staphylococcus aureus; Stress; Surface; System; Techniques; Testing; Time; Treatment Protocols; Universities; Woman; Work; antimicrobial; base; cell injury; clinical practice; combat; fluid flow; fluorescence microscope; improved; innovation; medical schools; meetings; methicillin resistant Staphylococcus aureus; novel; novel diagnostics; pathogen; pathogenic bacteria; public health relevance; rapid detection; repair enzyme; repaired; resistant strain; shear stress; sobriety; statistics; trend

DESCRIPTION (provided by applicant): The emergence of bacterial resistance to antibiotics continues to be a significant public health challenge. Factors contributing to the rise in antibiotic resistance include widespread and inappropriate prescription of broad spectrum antibiotics and patient non-compliance to antibiotic regiments. The healthcare community is responding by limiting antibiotics and prescribing targeted narrow-spectrum antimicrobial therapies when possible. Meanwhile, current antimicrobial development is focused more and more on narrow-spectrum drugs. To enable the effective use of antimicrobial therapy, new methods for detection of antibiotic susceptibility must be developed that enable physicians to prescribe these narrow spectrum antibiotics as close to initial examination as possible. Here, we propose to investigate a novel mechanism that would be the basis for a diagnostic to meet this important public health need. In this R21 application, Dr. Alexis Sauer-Budge at the Fraunhofer Center for Manufacturing Innovation at Boston University and Dr. Jean Lee of Brigham and Women's Hospital and Harvard Medical School have teamed up to explore the hypothesis that mechanical stress on bacteria will damage the cell wall and rapidly initiate cell wall repair biosynthesis pathways. In the presence of antibiotics targeted at cell wall biosynthesis, susceptible strains will be unable to recover from the damage and will die, whereas resistant strains will recover. The susceptibility of the bacteria can therefore be determined rapidly via fluorescence microscopy when the mechanical stress is applied in the presence of fluorescent dyes which stain the damaged bacteria. We propose to investigate this hypothesis by building a flow cell and optical apparatus, varying experimental conditions to optimize the protocol for antibiotic susceptibility detection, and quantify the variability due to different strains and growth phases of the bacteria. We propose to use the model system of Staphylococcus aureus, both methicillin-susceptible and methicillin- resistant strains. If successful, we anticipate this methodology will be applicable to a wide range of bacteria and antibiotics of various mechanisms of action. PUBLIC HEALTH RELEVANCE: The increasing prevalence of multi-drug resistant bacterial infections is a growing public health problem. To combat the trend and to fully enable physicians to prescribe appropriate antimicrobial therapy, new rapid diagnostic methods for antibiotic susceptibility must be developed. Here, we propose to address the gap in antibiotic susceptibility diagnostics by developing a novel technique for rapid detection of antibiotic susceptibility using Staphylococcus aureus as our model system.

描述（由申请人提供）：细菌对抗生素耐药性的出现仍然是一个重大的公共卫生挑战。导致抗生素耐药性上升的因素包括广泛和不适当的广谱抗生素处方以及患者不遵守抗生素方案。医疗保健界正在通过限制抗生素和处方有针对性的窄谱抗菌药物治疗来应对。同时，目前的抗菌药物开发越来越集中在窄谱药物上。为了使抗菌治疗的有效使用，必须开发新的方法来检测抗生素敏感性，使医生能够处方这些窄谱抗生素尽可能接近初步检查。在这里，我们建议研究一种新的机制，这将是诊断的基础，以满足这一重要的公共卫生需求。在这款R21应用中，波士顿大学弗劳恩霍夫制造业创新中心的Alexis Sauer-Budge博士和布里格姆妇女医院及哈佛医学院的Jean Lee博士联手探索了一个假说，即对细菌的机械应力会破坏细胞壁，并迅速启动细胞壁修复生物合成途径。在靶向细胞壁生物合成的抗生素存在下，敏感菌株将无法从损伤中恢复并死亡，而抗性菌株将恢复。因此，当在存在染色受损细菌的荧光染料的情况下施加机械应力时，可以通过荧光显微镜快速确定细菌的易感性。我们建议通过建立流动池和光学装置，改变实验条件来优化抗生素敏感性检测的方案，并量化由于细菌的不同菌株和生长阶段而引起的变异性来研究这一假设。我们建议使用金黄色葡萄球菌的模型系统，包括甲氧西林敏感菌株和甲氧西林耐药菌株。如果成功，我们预计这种方法将适用于各种作用机制的细菌和抗生素。公共卫生相关性：多重耐药细菌感染的日益普遍是一个日益严重的公共卫生问题。为了对抗这一趋势，并充分使医生能够处方适当的抗菌治疗，必须开发新的快速诊断抗生素敏感性的方法。在这里，我们建议通过开发一种新的技术来快速检测抗生素敏感性，使用金黄色葡萄球菌作为我们的模型系统，以解决抗生素敏感性诊断的差距。