Gene expression in S aureus biofilms

金黄色葡萄球菌生物膜中的基因表达

• 批准号: 6851133
• 负责人: KIMBERLY Kay JEFFERSON
• 金额: $ 16万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6851133
• 关键词: antibiotics; biofilm; gene expression; genes; infection; stress

DESCRIPTION (provided by applicant): The long-term objective of this project is to characterize the properties of staphylococcal biofilms that account for their resistance to antimicrobial chemotherapy. S. aureus is an important cause of biofilm-related infections such as native valve endocarditis, osteomyelitis, and medical device-related infections. Infections involving staphylococcal biofilms are often very difficult to treat with antibiotics and may be recurrent. The characteristics of biofilms that make them refractory to antibiotic therapy are not well understood at this time. In this study the role of gene regulation or "transcriptional adaptation" in the resistance of biofilms to antibiotics will be analyzed. One untested possibility is that biofilms are more resistant to antibiotics than planktonic cells because they are "hyper-adaptable" or uniquely poised to respond to stressful environmental conditions through the rapid transcriptional activation of stress-related genes. An alternative hypothesis is that cells within a biofilm have more time to respond at the transcriptional level to antibiotics than do their planktonic counterparts due to diffusion limitations imparted by the exopolysaccharide matrix. Both of these hypotheses challenge the common notion that the properties that make biofilms resistant to antibiotics are constitutive rather than induced following antibiotic exposure. In order to test these hypotheses, a global screen of genes activated in planktonic cells and biofilms in response to antibiotics from three distinct classes will be conducted by microarray analysis. Genes that are significantly induced or repressed in response to antibiotic treatment will be further characterized by mutagenesis. It is hoped that a better understanding of the mechanism of antibiotic resistance of biofilms will advance the development of therapies used to combat these infections and it is expected that these studies will increase our current knowledge of the regulation of the stress response.

描述（由申请人提供）：该项目的长期目标是表征葡萄球菌生物膜的特性，这些特性解释了它们对抗菌化疗的抗性。金黄色葡萄球菌是与生物膜相关感染的重要原因，例如天然瓣膜性心内膜炎，骨髓炎和与医疗器械相关的感染。涉及葡萄球菌生物膜的感染通常很难用抗生素治疗，并且可能会复发。目前尚不清楚生物膜使其对抗生素治疗难治性的特征。在这项研究中，将分析基因调节或“转录适应”在生物膜对抗生素的抗性中的作用。一种未经测试的可能性是，与浮游细胞相比，生物膜对抗生素具有更大的抵抗力，因为它们“过度适应”或独特地通过通过应激相关基因的快速转录激活来应对压力环境条件。另一种假设是，生物膜内的细胞在转录水平上对抗生素的反应比其浮游物质的膨胀局限性赋予了exopolysaccharide矩阵，因此在转录水平上对抗生素有反应。这两个假设都挑战了使抗生素具有抗性生物膜的特性是组成型的，而不是抗生素暴露后引起的。为了检验这些假设，将通过微阵列分析对三种不同类别的抗生素进行激活的基因和生物膜中激活的基因筛选。因抗生素治疗而受到显着诱导或抑制的基因将以诱变为特征。希望对生物膜抗生素抗性的机制有更好的理解将推动用于打击这些感染的疗法的发展，并且可以预期，这些研究将增加我们当前对压力反应调节的了解。