条件感染导致的死亡率高，临床危害巨大，然而其发病机制至今未能完全解析。申请人前期研究发现条件感染部位的氧化压力增加且条件致病菌抗氧化压力能力更高，因而推测氧化压力增高导致的局部微生态物种组成向耐氧化压力迁移是导致条件致病菌定植人体和造成感染的前提“条件”。本研究计划通过分析慢性阻塞性肺病（COPD）条件感染过程中局部氧化压力、微生态宏基因组和宏转录组的动态变化和功能基因表达，以及通过支气管类器官微流控芯片技术在体外重建呼吸道微生态，实时观察其在不同氧化压力下的变化，验证氧化压力与微生态失衡和条件致病菌定植感染的关联。本研究如能明确氧化压力升高在条件感染发病机制中的重要作用，将为临床条件感染的预测、诊断、寻找抗生素以外的治疗策略提供新的方法和思路。

Opportunistic infections are common in clinical practice and often lead to death, while the underlying mechanism remains unclarified. Our previous study has found increased reactive oxygen species (ROS) concentration in the infectious sites, and opportunistic pathogens often have higher anti-oxidative capacity than commensals and classical pathogens. Thus, we propose that the shift to a ROS-resistant microbiome due to the increased local ROS stress recruit ROS-resistant opportunistic pathogens as new members predisposed their infections. In this proposal, we plan to verify the causal relation between increased ROS level and microbiome dysbiosis and colonization of opportunistic pathogens through metagenome and metatranscriptome sequencing of dynamic samples of opportunistic infections in patients of chronic obstructive pulmonary disease (COPD), where we would investigate the regulation network of anti-oxidative stress response and clarify all genes of the pathogens involved in the response to oxidative stress. Finally, we are going to reconstruct the respiratory microbiome from COPD patients on a bronchus-on-chip, and observe its alterations under various ROS level. The key role of ROS in the mechanism of opportunistic infection if verified as we propose, will provide novel resolutions for the prediction, prevention, and treatment of opportunistic infections other than antibiotics.