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Review 1: "Nosocomial Pseudomonas aeruginosaregulates alginate biosynthesis and Type VI secretion system during adaptive and convergent evolution for coinfection in critically ill COVID-19 patients"

Published onApr 14, 2022
Review 1: "Nosocomial Pseudomonas aeruginosaregulates alginate biosynthesis and Type VI secretion system during adaptive and convergent evolution for coinfection in critically ill COVID-19 patients"
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key-enterThis Pub is a Review of
Nosocomial <i>Pseudomonas aeruginosa</i> regulates alginate biosynthesis and Type VI secretion system during adaptive and convergent evolution for coinfection in critically ill COVID-19 patients
Description

AbstractCOVID-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 P. aeruginosa isolated from two critical COVID-19 patients in this study. We sequenced and compared the genomes and transcriptomes of P. aeruginosa isolates longitudinally and parallelly for its evolutionary traits. P. 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 P. aeruginosa reduced its virulence towards both prokaryotic competitors and eukaryotic host through inhibiting its T6SS during evolution. P. aeuginosa 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 P. aeruginosa coinfection in COVID-19 patient.

RR:C19 Evidence Scale rating by reviewer:

  • Misleading. Serious flaws and errors in the methods and data render the study conclusions misinformative. The results and conclusions of the ideal study are at least as likely to conclude the opposite of its results and conclusions than agree. Decision-makers should not consider this evidence in any decision.

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Review:

This manuscript describes what is stated as the “evolution of Pseudomonas aeruginosa within two different COVID-19 patients” by performing a comprehensive genomic and transcriptomic analysis and a few assays of two different strains isolated a few days apart. The genomic/transcriptomic characterization is standard and for the most part adequate, however, the conclusions drawn from this analysis regarding their importance, as well as that of the various phenotypes (mucoid, decreased type VI secretion) in the context of COVID-19 co-infection, is vastly overinterpreted based on the data presented.

In particular, since only a single colony was picked at each time point, it is not clear whether the strains with the “evolved” genotype/phenotype might have been present at the initial time and just not picked. And similarly, colonies with the “initial” genotype/phenotype might have been present at a later time, but only the mucoid colonies were picked. To make grand statements about why these strains survived based on single colonies would seem to greatly overstate these findings in the context of COVID-19 co-infection.

Also, there should be more description of where the strains came from and the clinical condition of the COVID-19 patient at the time of isolation. It is stated that P. aeruginosa was isolated from sputum or bronchoalveolar lavage fluid, but it should be made clear which strain was derived from which type of sample. Also, whether the patient was treated with an antibiotic should be presented as this may be relevant for the emergence of antibiotic resistance. Other major issues relate to the assays that were performed (colony morphology, biofilms, bacterial competition assay, and macrophage cytotoxicity); in each case, there would appear to be no positive or negative controls included.

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