Persistent Bacterial Coinfection of a COVID-19 Patient Caused by a Genetically Adapted Pseudomonas aeruginosa Chronic Colonizer

Frontiers in Cellular and Infection Microbiology

Zhaofang Jiang¹  Jiuxin Qu¹  Lei Liu²  Yingxia Liu²  Yang Liu³  Zhao Cai⁴  Xiangke Duan⁴  Yuao Zhu⁴  Shuhong Han⁴  Yingdan Zhang⁴  Yumei Liu⁴  Jihong Liu⁵  Liang Yang⁶  Chao Zhuo⁷ 

[1] Department of Clinical Laboratory, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China;Department of Clinical Laboratory, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China;Shenzhen Key Laboratory of Pathogen and Immunity, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China;Medical Research Center, Southern University of Science and Technology Hospital, Shenzhen, China;School of Medicine, Southern University of Science and Technology, Shenzhen, China;School of Medicine, Southern University of Science and Technology, Shenzhen, China;Medical Research Center, Southern University of Science and Technology Hospital, Shenzhen, China;School of Medicine, Southern University of Science and Technology, Shenzhen, China;Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Southern University of Science and Technology, Shenzhen, China;The State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;

关键词: Pseudomonas aeruginosa;    COVID-19;    biofilm;    coinfection;    DNA methylation;   

DOI  :  10.3389/fcimb.2021.641920

来源: Frontiers

【 摘 要 】

Pseudomonas aeruginosa is a biofilm-forming opportunistic pathogen which causes chronic infections in immunocompromised patients and leads to high mortality rate. It is identified as a common coinfecting pathogen in COVID-19 patients causing exacerbation of illness. In our hospital, P. aeruginosa is one of the top coinfecting bacteria identified among COVID-19 patients. We collected a strong biofilm-forming P. aeruginosa strain displaying small colony variant morphology from a severe COVID-19 patient. Genomic and transcriptomic sequencing analyses were performed with phenotypic validation to investigate its adaptation in SARS-CoV-2 infected environment. Genomic characterization predicted specific genomic islands highly associated with virulence, transcriptional regulation, and DNA restriction-modification systems. Epigenetic analysis revealed a specific N6-methyl adenine (m6A) methylating pattern including methylation of alginate, flagellar and quorum sensing associated genes. Differential gene expression analysis indicated that this isolate formed excessive biofilm by reducing flagellar formation (7.4 to 1,624.1 folds) and overproducing extracellular matrix components including CdrA (4.4 folds), alginate (5.2 to 29.1 folds) and Pel (4.8–5.5 folds). In summary, we demonstrated that P. aeuginosa clinical isolates with novel epigenetic markers could form excessive biofilm, which might enhance its antibiotic resistance and in vivo colonization in COVID-19 patients.

【 授权许可】

CC BY