Abstract
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.
Highlights
Coronavirus Disease 2019 (COVID-19) is a fatal lung infection caused by the novel coronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which has influenced millions of people globally since its onset
P. aeruginosa was highly associated with the bacterial coinfection induced in the patients during critical stage of COVID-19
We characterized two P. aeruginosa small colony variant (SCV) isolated from respiratory samples of one critical COVID-19 patient on genomic, transcriptomic, and phenotypic levels for their adaptation and underlying mechanisms causing bacterial coinfection
Summary
Coronavirus Disease 2019 (COVID-19) is a fatal lung infection caused by the novel coronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which has influenced millions of people globally since its onset. Higher mortality rate was observed from COVID-19 patients with older age and underlying diseases (Liu et al, 2020; Wang T. et al, 2020; Zhou et al, 2020) Such viral lung infection weakens host immunity and alters the composition and functions of respiratory microbiota, predisposing hosts to bacterial coinfections (Hanada et al, 2018). Expression of las and rhl quorum sensing genes were significantly elevated This is opposite from previous studies that P. aeruginosa attenuates its quorum sensing systems in the biofilm for escaping from host immune clearance (Marvig et al, 2015; Wang et al, 2017). This study demonstrated that P. aeruginosa adopts complex genetic adaptations in the SARS-CoV-2 infected environment for higher antimicrobial resistance, persistent colonization and disease induction. Our findings contribute to the prognosis of disease development and treatment decision to manage P. aeruginosa coinfection in COVID-19 patients
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