4.7 Article

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

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2021.641920

Keywords

Pseudomonas aeruginosa; COVID-19; biofilm; coinfection; DNA methylation

Funding

  1. Guangdong Natural Science Foundation for Distinguished Young Scholar [2020B1515020003]
  2. Start-up Grants from the Southern University of Science and Technology (SUSTech) [Y01416106, Y01416206]
  3. Science and Technology Program of Shenzhen [JCYJ20190809144005609]
  4. Guangdong Basic and Applied Basic Research Foundation [2020A1515010586, 2019A1515110640]
  5. Guangzhou Municipal Science and Technology Bureau [201607020044]
  6. Bill & Melinda Gates Foundation
  7. Natural Science Fund of Guangdong Province [2020A1515010316]

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The study found that a strong biofilm-forming Pseudomonas aeruginosa strain collected from a severe COVID-19 patient displayed specific epigenetic markers, which might enhance its antibiotic resistance and in vivo colonization ability in COVID-19 patients.
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 N-6-methyl adenine (m(6)A) 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.

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