Qu Jiuxin, Cai Zhao, Duan Xiangke, Zhang Han, Cheng Hang, Han Shuhong, Yu Kaiwei, Jiang Zhaofang, Zhang Yingdan, Liu Yang, Bai Fang, Liu Yingxia, Liu Lei, Yang Liang
Department of Clinical Laboratory, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Guangdong Provincial Clinical Research Center for Infectious Diseases (Tuberculosis), National Clinical Research Center for Infectious Diseases, Shenzhen, 518000, Guangdong, China.
School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.
Cell Biosci. 2022 Feb 9;12(1):14. doi: 10.1186/s13578-022-00748-z.
COVID-19 pneumonia has caused huge impact on the health of infected patients and associated with high morbidity and mortality. Shift in the lung microbial ecology upon such viral infection often worsens the disease and increases host susceptibility to superinfections. Bacterial superinfection contributes to the aggravation of COVID-19 and poses a great challenge to clinical treatments. An in-depth investigation on superinfecting bacteria in COVID-19 patients might facilitate understanding of lung microenvironment post virus infections and superinfection mechanism.
We analyzed the adaptation of two pairs of P. aeruginosa strains with the same MLST type isolated from two critical COVID-19 patients by combining sequencing analysis and phenotypic assays. Both P. aeruginosa strains were found to turn on alginate biosynthesis and attenuate type VI secretion system (T6SS) during short-term colonization in the COVID-19 patients, which results in excessive biofilm formation and virulence reduction-two distinct markers for chronic infections. The macrophage cytotoxicity test and intracellular reactive oxygen species measurement confirmed that the adapted P. aeruginosa strains reduced their virulence towards host cells and are better to escape from host immune clearance than their ancestors.
Our study suggests that SARS-CoV-2 infection can create a lung environment that allow rapid adaptive evolution of bacterial pathogens with genetic traits suitable for chronic infections.
新型冠状病毒肺炎（COVID-19）对感染患者的健康造成了巨大影响，且发病率和死亡率很高。病毒感染后肺部微生物生态的改变往往会使病情恶化，并增加宿主对重叠感染的易感性。细菌重叠感染会导致COVID-19病情加重，给临床治疗带来巨大挑战。深入研究COVID-19患者中的重叠感染细菌可能有助于了解病毒感染后的肺部微环境和重叠感染机制。
我们通过结合测序分析和表型分析，分析了从两名重症COVID-19患者中分离出的两对具有相同多位点序列分型（MLST）类型的铜绿假单胞菌菌株的适应性。发现这两株铜绿假单胞菌在COVID-19患者体内短期定植期间均开启藻酸盐生物合成并减弱VI型分泌系统（T6SS），这导致生物膜过度形成和毒力降低——这是慢性感染的两个不同标志。巨噬细胞细胞毒性试验和细胞内活性氧测量证实，适应性铜绿假单胞菌菌株对宿主细胞的毒力降低，并且比其祖先更能逃避宿主免疫清除。
我们的研究表明，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染可创造一个肺部环境，使具有适合慢性感染遗传特征的细菌病原体能够快速适应性进化。
