人类抗微生物感染的主要武器是抗生素。但随着抗生素的广泛应用，细菌耐药性成为了严峻挑战。人类迫切需要寻找更多有效的抗感染手段。噬菌体是细菌的病毒，有望成为又一种抗感染手段。但可以想象，随着噬菌体治疗在实践中的应用，噬菌体耐受又会成为严峻问题。及早研究噬菌体耐受有着极为重要的意义。我们已经发现铜绿假单胞菌PA1的噬菌体受体为LPS；细菌可通过丢失大片段DNA,从而丢失噬菌体受体这样一种“断臂求生”机制建立噬菌体耐受。本项目旨在探讨另一种没有DNA大片段缺失的菌株PA1ar耐受噬菌体的另样机制，全面考察众多LPS合成相关基因中，哪些基因的缺失或突变有可能导致细菌LPS变异，进而导致噬菌体耐受。勾画出细菌经过不同基因缺失或突变，殊途同归，最终导致LPS及其受体改变，建立噬菌体耐受的新机制，为未来的噬菌体治疗奠定理论基础。项目虽以铜绿假单胞菌为研究对象，但对于探讨其他细菌的噬菌体耐受具有借鉴意义。

Antibiotic therapy is obviously the most important weapon against bacterial infections for human bing. However, antibiotic resistance is becoming very rigorous problem as antibiotics are widely used in clinic practice. Almost no antibiotics can be chosed for treatment for some bacterial infections caused by superbugs or multi-drug resisitant pathogens. So, humans have to keep seeking for other new weapons against bacterial infections. Bacteriophages are viruses of bacteria and phage therapy is potentially application perspective. But it can be imagined that phage resistance of bacteria will be another tough problem as phage therapy is widely used in practice. Therefore, prospective investigations of phage resistance of bacteria are obviously significant. We had reported that phage receptor of Pseudomonas aeruginosa is chemically LPS and P. aeruginosa can become resistant to phage PaP1 infection by deleting a big DNA fragment (219.6 Kb) and hence losing the gene galU which is a key gene for LPS synthesis. We call this mechanism of bacterium resistance to phage as “cutting an arm for survival”. Based on above mentions, this project is focus on investigation of alterative mechanism of another phage-resistant mutant PA1ar which has been confirmed no deletion of big DNA fragment and no loss of gene galU. Obviously, this phage resistant mutant must have different resistant mechanism. The purpose of the project is trying to validate deletion or mutation of what gene among many genes related to LPS synthesis pathways will cause loss of LPS and phage receptor of host bacteria. For different strain of host bacteria, although deletion or mutation of different gene probably occur but all lead to same consequence, that is resistance of host bacteria to phages. Completion of this project will lay theory foundation for phage therapy. Although using P.aeruginosa as research object, completion of this project is also significant reference to study of phage resistant mechanism for other different bacteria.