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Catabolism of Nucleic Acids by a Cystic Fibrosis Pseudomonas aeruginosa Isolate: An Adaptive Pathway to Cystic Fibrosis Sputum Environment
Pseudomonas aeruginosa is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). We undertook Biolog Phenotype Microarray testing of P. aeruginosa CF isolates to investigate their catabolic capabilities compared to P. aeruginosa laboratory strains PAO1 and PA14. One strain,...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555301/ https://www.ncbi.nlm.nih.gov/pubmed/31214142 http://dx.doi.org/10.3389/fmicb.2019.01199 |
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author | Kumar, Sheemal Shanista Penesyan, Anahit Elbourne, Liam Davin Hunt Gillings, Michael R. Paulsen, Ian T. |
author_facet | Kumar, Sheemal Shanista Penesyan, Anahit Elbourne, Liam Davin Hunt Gillings, Michael R. Paulsen, Ian T. |
author_sort | Kumar, Sheemal Shanista |
collection | PubMed |
description | Pseudomonas aeruginosa is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). We undertook Biolog Phenotype Microarray testing of P. aeruginosa CF isolates to investigate their catabolic capabilities compared to P. aeruginosa laboratory strains PAO1 and PA14. One strain, PASS4, displayed an unusual phenotype, only showing strong respiration on adenosine and inosine. Further testing indicated that PASS4 could grow on DNA as a sole carbon source, with a higher biomass production than PAO1. This suggested that PASS4 was specifically adapted to metabolize extracellular DNA, a substrate present at high concentrations in the CF lung. Transcriptomic and proteomic profiling of PASS4 and PAO1 when grown with DNA as a sole carbon source identified a set of upregulated genes, including virulence and host-adaptation genes. PASS4 was unable to utilize N-Acetyl-D-glucosamine, and when we selected PASS4 mutants able to grow on this carbon source, they also displayed a gain in ability to catabolize a broad range of other carbon sources. Genome sequencing of the mutants revealed they all contained mutations within the purK gene, encoding a key protein in the de novo purine biosynthesis pathway. This suggested that PASS4 was a purine auxotroph. Growth assays in the presence of 2 mM adenosine and the complementation of PASS4 with an intact purK gene confirmed this conclusion. Purine auxotrophy may represent a viable microbial strategy for adaptation to DNA-rich environments such as the CF lung. |
format | Online Article Text |
id | pubmed-6555301 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65553012019-06-18 Catabolism of Nucleic Acids by a Cystic Fibrosis Pseudomonas aeruginosa Isolate: An Adaptive Pathway to Cystic Fibrosis Sputum Environment Kumar, Sheemal Shanista Penesyan, Anahit Elbourne, Liam Davin Hunt Gillings, Michael R. Paulsen, Ian T. Front Microbiol Microbiology Pseudomonas aeruginosa is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). We undertook Biolog Phenotype Microarray testing of P. aeruginosa CF isolates to investigate their catabolic capabilities compared to P. aeruginosa laboratory strains PAO1 and PA14. One strain, PASS4, displayed an unusual phenotype, only showing strong respiration on adenosine and inosine. Further testing indicated that PASS4 could grow on DNA as a sole carbon source, with a higher biomass production than PAO1. This suggested that PASS4 was specifically adapted to metabolize extracellular DNA, a substrate present at high concentrations in the CF lung. Transcriptomic and proteomic profiling of PASS4 and PAO1 when grown with DNA as a sole carbon source identified a set of upregulated genes, including virulence and host-adaptation genes. PASS4 was unable to utilize N-Acetyl-D-glucosamine, and when we selected PASS4 mutants able to grow on this carbon source, they also displayed a gain in ability to catabolize a broad range of other carbon sources. Genome sequencing of the mutants revealed they all contained mutations within the purK gene, encoding a key protein in the de novo purine biosynthesis pathway. This suggested that PASS4 was a purine auxotroph. Growth assays in the presence of 2 mM adenosine and the complementation of PASS4 with an intact purK gene confirmed this conclusion. Purine auxotrophy may represent a viable microbial strategy for adaptation to DNA-rich environments such as the CF lung. Frontiers Media S.A. 2019-05-31 /pmc/articles/PMC6555301/ /pubmed/31214142 http://dx.doi.org/10.3389/fmicb.2019.01199 Text en Copyright © 2019 Kumar, Penesyan, Elbourne, Gillings and Paulsen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Kumar, Sheemal Shanista Penesyan, Anahit Elbourne, Liam Davin Hunt Gillings, Michael R. Paulsen, Ian T. Catabolism of Nucleic Acids by a Cystic Fibrosis Pseudomonas aeruginosa Isolate: An Adaptive Pathway to Cystic Fibrosis Sputum Environment |
title | Catabolism of Nucleic Acids by a Cystic Fibrosis Pseudomonas aeruginosa Isolate: An Adaptive Pathway to Cystic Fibrosis Sputum Environment |
title_full | Catabolism of Nucleic Acids by a Cystic Fibrosis Pseudomonas aeruginosa Isolate: An Adaptive Pathway to Cystic Fibrosis Sputum Environment |
title_fullStr | Catabolism of Nucleic Acids by a Cystic Fibrosis Pseudomonas aeruginosa Isolate: An Adaptive Pathway to Cystic Fibrosis Sputum Environment |
title_full_unstemmed | Catabolism of Nucleic Acids by a Cystic Fibrosis Pseudomonas aeruginosa Isolate: An Adaptive Pathway to Cystic Fibrosis Sputum Environment |
title_short | Catabolism of Nucleic Acids by a Cystic Fibrosis Pseudomonas aeruginosa Isolate: An Adaptive Pathway to Cystic Fibrosis Sputum Environment |
title_sort | catabolism of nucleic acids by a cystic fibrosis pseudomonas aeruginosa isolate: an adaptive pathway to cystic fibrosis sputum environment |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555301/ https://www.ncbi.nlm.nih.gov/pubmed/31214142 http://dx.doi.org/10.3389/fmicb.2019.01199 |
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