Identifying genes associated with biofilm production in Pseudomonas aeruginosa

Jessica Chee
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Abstract

Pseudomonas aeruginosa is an opportunistic pathogen associated with a variety of life-threatening diseases. Infections caused by P. aeruginosa can be nearly untreatable because of its multidrug-resistance. One of the characteristics of P. aeruginosa that helps it survive in high drug concentrations is its ability to form biofilms–large communities of cells encompassed by extracellular polymeric substances that defend against many antibiotics. In fact, sub-minimum inhibitory concentrations of antibiotics stimulate biofilm production. This project aims to identify genes associated with biofilm induction in P. aeruginosa by screening a transposon mutant library for mutants that fail to show increased biofilm production when exposed to sub-minimum inhibitory concentrations of cefixime, tobramycin, and thiostrepton. So far, we have identified one gene, PA2714, that encodes a predicted molybdopterin oxidoreductase required for biofilm production. Because of the strong association between biofilm production and antibiotic tolerance in P. aeruginosa, the gene identified in this screen may be a useful therapeutic target for novel antimicrobialsthat can disrupt biofilm formation.
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铜绿假单胞菌生物膜生成相关基因的鉴定
铜绿假单胞菌是一种与多种危及生命的疾病相关的机会性病原体。铜绿假单胞菌引起的感染几乎无法治愈,因为它具有多重耐药性。铜绿假单胞菌在高浓度药物环境下存活的一个特点是其形成生物膜的能力——由细胞外聚合物质包围的大型细胞群落,可以抵抗许多抗生素。事实上,低于最低抑菌浓度的抗生素会刺激生物膜的产生。该项目旨在通过筛选转座子突变体文库来鉴定铜绿假单胞菌中与生物膜诱导相关的基因,这些突变体在暴露于低于最低抑制浓度的头孢克肟、妥布霉素和硫链霉素时不能显示出生物膜产生的增加。到目前为止,我们已经确定了一个基因PA2714,该基因编码生物膜生产所需的钼酸盐氧化还原酶。由于铜绿假单胞菌的生物膜生成与抗生素耐受性之间存在很强的相关性,因此在该筛选中发现的基因可能是开发破坏生物膜形成的新型抗菌剂的有用靶点。
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