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Emerging Phage Resistance in Pseudomonas aeruginosa PAO1 Is Accompanied by an Enhanced Heterogeneity and Reduced Virulence

Bacterial surface structures of a proteinic nature and glycoconjugates contribute to biofilm formation and provide shields to host defense mechanisms (e.g., the complement system and phagocytosis). A loss or alteration of these molecules, leading to phage resistance, could result in fewer virulent b...

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Autores principales: Markwitz, Pawel, Olszak, Tomasz, Gula, Grzegorz, Kowalska, Magdalena, Arabski, Michal, Drulis-Kawa, Zuzanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310095/
https://www.ncbi.nlm.nih.gov/pubmed/34372538
http://dx.doi.org/10.3390/v13071332
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author Markwitz, Pawel
Olszak, Tomasz
Gula, Grzegorz
Kowalska, Magdalena
Arabski, Michal
Drulis-Kawa, Zuzanna
author_facet Markwitz, Pawel
Olszak, Tomasz
Gula, Grzegorz
Kowalska, Magdalena
Arabski, Michal
Drulis-Kawa, Zuzanna
author_sort Markwitz, Pawel
collection PubMed
description Bacterial surface structures of a proteinic nature and glycoconjugates contribute to biofilm formation and provide shields to host defense mechanisms (e.g., the complement system and phagocytosis). A loss or alteration of these molecules, leading to phage resistance, could result in fewer virulent bacteria. In this study, we evaluate the biology and phenotype changes in Pseudomonas aeruginosa PAO1 phage-resistant clones, which emerge in phage-treated biofilms. We characterize these clones for phage-typing patterns, antibiotic resistance, biofilm formation, pathogenicity, and interactions with the innate immune system. Another important question that we address is whether phage-resistant mutants are also generated incidentally, despite the phage treatment-selective pressure, as the natural adaptation of the living biofilm population. It is found that the application of different phages targeting a particular receptor selects similar phage resistance patterns. Nevertheless, this results in a dramatic increase in the population heterogeneity, giving over a dozen phage-typing patterns, compared to one of the untreated PAO1 sessile forms. We also confirm the hypothesis that “phage-resistant bacteria are more susceptible to antibiotics and host-clearance mechanisms by the immune system”. These findings support phage application in therapy, although the overall statement that phage treatment selects the less virulent bacterial population should be further verified using a bigger collection of clinical strains.
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spelling pubmed-83100952021-07-25 Emerging Phage Resistance in Pseudomonas aeruginosa PAO1 Is Accompanied by an Enhanced Heterogeneity and Reduced Virulence Markwitz, Pawel Olszak, Tomasz Gula, Grzegorz Kowalska, Magdalena Arabski, Michal Drulis-Kawa, Zuzanna Viruses Article Bacterial surface structures of a proteinic nature and glycoconjugates contribute to biofilm formation and provide shields to host defense mechanisms (e.g., the complement system and phagocytosis). A loss or alteration of these molecules, leading to phage resistance, could result in fewer virulent bacteria. In this study, we evaluate the biology and phenotype changes in Pseudomonas aeruginosa PAO1 phage-resistant clones, which emerge in phage-treated biofilms. We characterize these clones for phage-typing patterns, antibiotic resistance, biofilm formation, pathogenicity, and interactions with the innate immune system. Another important question that we address is whether phage-resistant mutants are also generated incidentally, despite the phage treatment-selective pressure, as the natural adaptation of the living biofilm population. It is found that the application of different phages targeting a particular receptor selects similar phage resistance patterns. Nevertheless, this results in a dramatic increase in the population heterogeneity, giving over a dozen phage-typing patterns, compared to one of the untreated PAO1 sessile forms. We also confirm the hypothesis that “phage-resistant bacteria are more susceptible to antibiotics and host-clearance mechanisms by the immune system”. These findings support phage application in therapy, although the overall statement that phage treatment selects the less virulent bacterial population should be further verified using a bigger collection of clinical strains. MDPI 2021-07-10 /pmc/articles/PMC8310095/ /pubmed/34372538 http://dx.doi.org/10.3390/v13071332 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Markwitz, Pawel
Olszak, Tomasz
Gula, Grzegorz
Kowalska, Magdalena
Arabski, Michal
Drulis-Kawa, Zuzanna
Emerging Phage Resistance in Pseudomonas aeruginosa PAO1 Is Accompanied by an Enhanced Heterogeneity and Reduced Virulence
title Emerging Phage Resistance in Pseudomonas aeruginosa PAO1 Is Accompanied by an Enhanced Heterogeneity and Reduced Virulence
title_full Emerging Phage Resistance in Pseudomonas aeruginosa PAO1 Is Accompanied by an Enhanced Heterogeneity and Reduced Virulence
title_fullStr Emerging Phage Resistance in Pseudomonas aeruginosa PAO1 Is Accompanied by an Enhanced Heterogeneity and Reduced Virulence
title_full_unstemmed Emerging Phage Resistance in Pseudomonas aeruginosa PAO1 Is Accompanied by an Enhanced Heterogeneity and Reduced Virulence
title_short Emerging Phage Resistance in Pseudomonas aeruginosa PAO1 Is Accompanied by an Enhanced Heterogeneity and Reduced Virulence
title_sort emerging phage resistance in pseudomonas aeruginosa pao1 is accompanied by an enhanced heterogeneity and reduced virulence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310095/
https://www.ncbi.nlm.nih.gov/pubmed/34372538
http://dx.doi.org/10.3390/v13071332
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