Antibiotic resistance of S. aureus biofilms

描述（由申请人提供）：S。金黄色葡萄球菌是生物膜相关感染如心内膜炎、慢性骨髓炎、涉及透镜植入物的角膜感染和医疗装置相关感染的重要原因。涉及葡萄球菌生物膜的感染通常很难用抗生素治疗，并且可能复发或需要手术切除受感染的器械或组织。临床实验室中使用的抗生素敏感性试验测量的是浮游菌或自由漂浮菌的耐药性，而不能解释S。金黄色葡萄球菌生物膜对大多数抗生素的耐药性明显高于嗜热细菌。生物膜的特点，使他们难治性抗生素治疗是不是很清楚在这个时候。该项目的长期目标是描述葡萄球菌生物膜的特性，这些特性使其对抗菌化疗难以耐受。该项目的近期目标是评估聚N-乙酰葡萄糖胺（PNAG）在抗生素耐药性中的作用，PNAG在S.金黄色葡萄球菌生物膜形成。首先，将表征PNAG表达对细菌抗生素抗性的影响。接下来，将实施基于细菌通过蛋白A /Fc-受体相互作用的交联的PNAG-独立的生物膜模型，使得PNAG在生物膜抗生素抗性中的作用可以与其在生物膜形成中的作用分开。此外，将通过共聚焦显微镜分析PNAG对荧光标记的抗生素在整个生物膜中的渗透的影响。最后，对PNAG与常用抗生素的相互作用进行了研究。将表征金黄色葡萄球菌感染。我们推测PNAG在S.金黄色葡萄球菌生物膜作为物理屏障阻止抗生素渗透，并期望了解PNAG在金黄色葡萄球菌生物膜中作用。金黄色葡萄球菌生物膜对抗生素的抗性将促进用于对抗这些感染的疗法的发展。

DESCRIPTION (provided by applicant): S. aureus is an important cause of biofilm-related infections such as endocarditis, chronic osteomyelitis, corneal infections involving lens implants, and medical device-related infections. Infections involving staphylococcal biofllms are often very difficult to treat with antibiotics and may be recurrent or require surgical removal of the infected device or tissue. Antibiotic susceptibility tests used in the clinical laboratory measure the resistance of planktonic or free-floating bacteria and do not account for the fact that S. aureus biofilms are significantly more resistant to most antibiotics than planktonic bacteria. The characteristics of biofilms that make them refractory to antibiotic therapy are not well understood at this time. The long-term objective of this project is to characterize the properties of staphylococcal biofilms that make them refractory to antimicrobial chemotherapy. The immediate goal of the proposed project is to assess the role in antibiotic resistance of poly-N-acetyl glucosamine (PNAG), which plays a critical role in S. aureus biofilm formation. First, the influence of PNAG expression on antibiotic resistance of planktonic bacteria will be characterized. Next, a PNAG-independent biofilm model, based on the cross linking of bacteria via protein A / Fc-receptor interactions, will be implemented so that the role of PNAG in biofilm antibiotic resistance can be separated from its role in biofilm formation. In addition, the effect of PNAG on the penetration of fluorescently labeled antibiotics throughout biofilms will be analyzed by confocal microscopy. Finally, the interaction between PNAG and antibiotics commonly used to treat S. aureus infections will be characterized. We hypothesize that PNAG plays an important role in the resistance of S. aureus biofilms by acting as a physical barrier against antibiotic penetration and expect that knowledge of the role of PNAG in S. aureus biofilm resistance to antibiotics will advance the development of therapies used to combat these infections.