GENE EXPRESSION OF P AERUGINOSA DURING BIOFILM DEVELOPME

铜绿假单胞菌在生物膜发育过程中的基因表达

• 批准号: 6632195
• 负责人: MICHAEL J FRANKLIN
• 金额: $ 22.64万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6632195
• 关键词: Pseudomonas aeruginosa; bacterial genetics; biofilm; cell adhesion; confocal scanning microscopy; fluorescence microscopy; gene expression; gene induction /repression; gene mutation; microorganism growth

Bacteria that cause infectious diseases often grow in biofilms where the bacterial cells and their extracellular polymers are attached to biological or non-biological surfaces. Bacteria growing in biofilms demonstrate a variety of phenotypic differences compared to the same strains growing planktonically, including increased resistances to antimicrobials and to phagocytosis. This proposal is designed to elucidate the molecular mechanisms that enable bacteria to grow in biofilms and cause chronic, debilitating infections. Much progress has been made on the mechanisms used by bacteria to adhere to surfaces. However, there is little information about the physiological changes in bacterial that occur following bacterial adhesion and during biofilm development. We developed novel in situ genetic and microscopic methods to characterize the changes in gene expression that mediate these phenotypic changes. Using these novel selections, we isolated nine clones with fusions to genes that demonstrated a five-fold to thirty-fold increase in gene expression, following attachment of the opportunistic pathogen Pseudomonas aeruginosa to a surface. The goals of this proposal are designed to: (i) characterize the pathogen Pseudomonas aeruginosa to a surface. The goals of this proposal are designed to: (i) characterize the products of these surface-growth induced genes (sgi), (ii) determine the survival advantage imparted by sgis during biofilm development, and (ii) identify other changes in gene expression including gene repression, that occur during biofilm development of P. aeruginosa. Information provided by this research will increase our understanding of the physiology of bacteria growing in biofilms. This information will provide important targets for anti-microbials , either through inhibition of sgis required for biofilm development, or through aberrant induction of genes normally repressed during biofilm growth.

导致传染病的细菌通常生长在生物膜中，细菌细胞及其胞外聚合物附着在生物或非生物表面。与在浮游植物中生长的相同菌株相比，在生物膜中生长的细菌显示出各种表型差异，包括对抗菌剂和吞噬作用的抵抗力增强。这一提议旨在阐明使细菌能够在生物膜中生长并导致慢性、衰弱感染的分子机制。细菌附着在表面的机制已经取得了很大进展。然而，关于细菌黏附后和生物膜发育过程中细菌的生理变化的信息很少。我们开发了新的原位遗传和显微方法来表征介导这些表型变化的基因表达的变化。使用这些新的选择，我们分离出9个与基因融合的克隆，这些克隆显示，在条件致病菌铜绿假单胞菌附着在表面后，基因表达增加了5倍至30倍。这项提案的目标是：(I)将病原体铜绿假单胞菌描述为表面。这项建议的目的是：(I)表征这些表面生长诱导基因(SGI)的产物，(Ii)确定SGI在生物膜发育过程中所赋予的生存优势，以及(Ii)确定在铜绿假单胞菌生物膜发育过程中发生的其他基因表达的变化，包括基因抑制。这项研究提供的信息将增加我们对生物膜中细菌生长的生理学的理解。这些信息将为抗微生物药物提供重要的靶点，要么是通过抑制生物膜发育所需的SGI，要么是通过异常诱导通常在生物膜生长过程中被抑制的基因。