膜孔蛋白OmpF是多种抗菌药进入细菌的主要通道，它的表达水平下调或氨基酸位点突变是导致细菌产生耐药的重要机制。然而，申请者在前期研究中首次发现了一种新型OmpF突变体（GenBank登录号JX393912），它在临床分离的产超广谱β-内酰胺酶（ESBLs）奇异变形杆菌中正常表达不但没有引起耐药性的显著升高,反而表现对氨曲南高度敏感。本研究拟通过同源重组技术，获得表达新型OmpF突变体的克隆株，根据生长曲线、时间-杀菌曲线、最低抑菌浓度、氨曲南渗透速率和单通道传导试验的测定，全面了解其生物学特性；拟通过同源建模技术，构建新型OmpF突变体结构的计算机模拟，并结合生物学特性，推测新型OmpF突变体的不同结构在氨曲南转运过程中所起的作用。本课题有助于了解新型OmpF突变体对氨曲南通透性大幅提高的机制，为将来针对多重耐药细菌的新药研发提供依据。

Owing to OmpF is the main channel allowing antibiotic to go through, decreasing expression or nucleic acid sequence mutating of ompF gene is the most important mechanism to cause resistant for bacteria. However, we found an OmpF mutant（GenBank number: JX393912）in a former investigation and increasing susceptibility for Aztreonam was observed in some producing ESBLs proteus mirabilis clinical isolates carrying this ompF mutatant gene. Our aim is to clone and expression this ompF mutant gene by Homologous recombination technology. Then biological properties will be determined and Aztreonam transport mechanism will be analysed by computer modeling. Our finding will contribute to produce novel antibiotics against resistant bacteria.