GENE EXPRESSION OF P AERUGINOSA DURING BIOFILM DEVELOPME

引起传染病的细菌通常生长在生物膜中，其中细菌细胞及其胞外聚合物附着于生物或非生物表面。在生物膜中生长的细菌与以螺旋方式生长的相同菌株相比表现出多种表型差异，包括对抗菌剂和吞噬作用的抗性增加。该提案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。关于细菌粘附于表面的机制已经取得了很大进展。然而，关于细菌粘附后和生物膜发育过程中发生的细菌生理变化的信息很少。我们开发了新的原位遗传和显微镜方法来表征介导这些表型变化的基因表达变化。使用这些新的选择，我们分离出9个克隆与融合的基因，表现出5倍至30倍的基因表达增加，以下附着的机会致病菌铜绿假单胞菌的表面。本提案的目标旨在：（i）表征表面的病原体铜绿假单胞菌。该提案的目标旨在：（i）表征这些表面生长诱导基因（sgi）的产物，（ii）确定sgi在生物膜发育期间赋予的生存优势，以及（ii）鉴定铜绿假单胞菌生物膜发育期间发生的基因表达的其他变化，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生理学的理解。这些信息将为抗微生物剂提供重要的靶点，通过抑制生物膜发育所需的sgi，或通过异常诱导生物膜生长期间通常被抑制的基因。

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.