钼酸盐转运体促进肺炎克雷伯菌慢性感染的分子机制及其表达调控机制

肺炎克雷伯菌（简称肺克）是医院感染和社区获得性感染的重要病原菌，其引起的慢性感染更加难以治疗，目前对肺克慢性感染的分子机制尚不清楚。研究发现细菌慢性感染与缺氧密切相关，钼酸盐转运体ModABC是细菌厌氧硝酸盐呼吸所必须，因此推测ModABC可能与肺克慢性感染相关，但分子机制尚未研究。前期研究发现，CRP基因敲除后ModA表达下调而ModE表达上调，同时不利于肺克厌氧生长。本课题将对ModABC促进肺克慢性感染的分子机制及表达调控机制进行研究。内容如下：构建modA敲除株及回补株，体内外研究ModA对肺克慢性感染的作用及机制；构建modE敲除株及回补株，研究ModE对ModA表达的调控作用及其对肺克慢性感染的影响；通过钨酸盐处理（体外、体内）探讨钨酸盐治疗肺克慢性感染的可能性。本研究的成功将有助于阐明肺克慢性感染的分子机制及为其治疗提供新思路。

Klebsiella pneumoniae (Kp) is an important pathogen for nosocomial infections and community-acquired infections, and the chronic infections caused by it are more difficult to treat. Currently, the molecular mechanism of chronic infection with Kp is unknown. Previous research found that chronic bacterial infection is closely related to hypoxia. The molybdate transporter ModABC is necessary for anaerobic nitrate respiration. Hence, it is speculated that ModABC may be associated with chronic infection with Kp, but its molecular mechanism is not clear. Our previous studies showed that ModA expression was down-regulated while ModE expression was up-regulated, and the anaerobic growth of Kp decreased, after CRP gene knockout. In the present project, we focus on the molecular mechanism and expression regulation mechanism of ModABC in promoting Kp chronic infection. This study includes: ①We construct modA-deletion mutant and complemented mutant to study the role of ModA on Kp chronic infection in vitro and in vivo; ②We construct modE-deletion mutant and complemented mutant to study the regulation of ModE on ModA expression and its effect on chronic infection; ③We investigate the possibility of tungstate treatment for chronic infection in vitro and in vivo. Our study will elucidate the molecular mechanism of chronic infection with Kp and provide new thoughts for its treatment.