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Nosocomial Pseudomonas aeruginosaregulates alginate biosynthesis and Type VI secretion system during adaptive and convergent evolution for coinfection in critically ill COVID-19 patients

By Jiu-Xin Qu, Zhao Cai, Xiangke Duan, Han Zhang, Shuhong Han, Kaiwei Yu, Zhaofang Jiang, Yingdan Zhang, Yang Liu, Yingxia Liu, Lei Liu, Liang Yang

Posted 11 Apr 2021
bioRxiv DOI: 10.1101/2021.04.09.439260

COVID-19 pandemic has caused millions of death globally and caused huge impact on the health of infected patients. Shift in the lung microbial ecology upon such viral infection often worsens the disease and increases host susceptibility to secondary infections. Recent studies have indicated that bacterial coinfection is an unignorable factor contributing to the aggravation of COVID-19 and posing great challenge to clinical treatments. However, there is still a lack of in-depth investigation on the coinfecting bacteria in COVID-19 patients for better treatment of bacterial coinfection. With the knowledge that Pseudomonas aeruginosa is one of the top coinfecting pathogens, we analyzed the adaptation and convergent evolution of nosocomial Pseudomonas aeruginosa isolated from two critical COVID-19 patients in this study. We sequenced and compared the genomes and transcriptomes of Pseudomonas aeruginosa isolates longitudinally and parallelly for its evolutionary traits. Pseudomonas aeruginosa overexpressed alginate and attenuated Type VI secretion system (T6SS) during coinfection for excessive biofilm formation and suppressed virulence. Results of bacterial competition assay and macrophage cytotoxicity test indicated that Pseudomonas aeruginosa reduced its virulence towards both prokaryotic competitors and eukaryotic host through inhibiting its T6SS during evolution. Pseudomonas aeruginosa T6SS is thus one of the reasons for its advantage to cause coinfection in COVID-19 patients while the attenuation of T6SS could cause a shift in the microecological composition in the lung. Our study will contribute to the development of therapeutic measures and the discovery of novel drug target to eliminate Pseudomonas aeruginosa coinfection in COVID-19 patient.

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