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

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.

Impact of SARS-CoV-2 Epidemic on Antimicrobial Resistance: A Literature Review

“…This is probably due to intrinsic characteristics of P. aeruginosa in terms of virulence, adaptability, and spreading features. Biofilm-forming properties of P. aeruginosa may be the cause of problematic chronic lung infections, particularly in COVID-19 patients who underwent mechanical ventilation [68]. In any case, differently from CRE and CRAB, current literature did not show a significant spread of CRPA in course of COVID-19, although it could still represent a major threat for some patients.…”

COVID-19 and Antimicrobial Resistance: Data from the Greek Electronic System for the Surveillance of Antimicrobial Resistance—WHONET-Greece (January 2018–March 2021)

“…However, in blood isolates, we found consistently high non-susceptibility rates for the aforementioned antibiotics during both pre-pandemic and pandemic periods. P. aeruginosa has been identified as a common coinfecting pathogen in COVID-19 patients causing exacerbation of illness [ 29 , 56 , 60 , 61 , 62 ]. P. aeruginosa has shown high resistance to many antibiotics used during the COVID-period, such as carbapenems [ 48 , 63 , 64 ] and amikacin [ 48 , 65 , 66 ].…”

Gut and airway microbiota and their role in COVID-19 infection and pathogenesis: a scoping review

“…The increase in opportunistic pathogens in the gut and in the airway during the course of COVID-19 also plays a significant role in worsening disease prognosis. Co-infection has been shown to be a key prognostic factor in COVID-19 [ 66 ]; for example, pulmonary aspergillosis was estimated to occur in 19–33% of COVID-19 patients [ 67 – 69 ], and was reported in two of the studies included in this review [ 29 , 31 ]; Pseudomonas is one of the most commonly reported pathogens isolated from COVID-19 patients with bacterial co-infection [ 70 ], which was reported in one study included in this review as well [ 37 ].…”