Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis Lungs
Type II toxin-antitoxin (TA) systems are most commonly composed of two genes encoding a stable toxin, which harms the cell, and an unstable antitoxin that can inactivate it. TA systems were initially characterized as selfish elements, but have recently gained attention for regulating general stress...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2017.01180/full |
| _version_ | 1828788676605247488 |
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| author | Sandra B. Andersen Sandra B. Andersen Melanie Ghoul Ashleigh S. Griffin Bent Petersen Helle K. Johansen Søren Molin |
| author_facet | Sandra B. Andersen Sandra B. Andersen Melanie Ghoul Ashleigh S. Griffin Bent Petersen Helle K. Johansen Søren Molin |
| author_sort | Sandra B. Andersen |
| collection | DOAJ |
| description | Type II toxin-antitoxin (TA) systems are most commonly composed of two genes encoding a stable toxin, which harms the cell, and an unstable antitoxin that can inactivate it. TA systems were initially characterized as selfish elements, but have recently gained attention for regulating general stress responses responsible for pathogen virulence, formation of drug-tolerant persister cells and biofilms—all implicated in causing recalcitrant chronic infections. We use a bioinformatics approach to explore the distribution and evolution of type II TA loci of the opportunistic pathogen, Pseudomonas aeruginosa, across longitudinally sampled isolates from cystic fibrosis lungs. We identify their location in the genome, mutations, and gain/loss during infection to elucidate their function(s) in stabilizing selfish elements and pathogenesis. We found (1) 26 distinct TA systems, where all isolates harbor four in their core genome and a variable number of the remaining 22 on genomic islands; (2) limited mutations in core genome TA loci, suggesting they are not under negative selection; (3) no evidence for horizontal transmission of elements with TA systems between clone types within patients, despite their ability to mobilize; (4) no gain and limited loss of TA-bearing genomic islands, and of those elements partially lost, the remnant regions carry the TA systems supporting their role in genomic stabilization; (5) no significant correlation between frequency of TA systems and strain ability to establish as chronic infection, but those with a particular TA, are more successful in establishing a chronic infection. |
| first_indexed | 2024-12-12T00:58:09Z |
| format | Article |
| id | doaj.art-2977ecacb7db43668c181be36c325f85 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-12T00:58:09Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-2977ecacb7db43668c181be36c325f852022-12-22T00:43:49ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-06-01810.3389/fmicb.2017.01180248678Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis LungsSandra B. Andersen0Sandra B. Andersen1Melanie Ghoul2Ashleigh S. Griffin3Bent Petersen4Helle K. Johansen5Søren Molin6Department of Zoology, University of OxfordOxford, United KingdomThe Novo Nordisk Foundation Center for Biosustainability, Technical University of DenmarkLyngby, DenmarkDepartment of Zoology, University of OxfordOxford, United KingdomDepartment of Zoology, University of OxfordOxford, United KingdomDepartment of Bio and Health Informatics, Technical University of DenmarkLyngby, DenmarkDepartment of Clinical Microbiology, RigshospitaletCopenhagen, DenmarkThe Novo Nordisk Foundation Center for Biosustainability, Technical University of DenmarkLyngby, DenmarkType II toxin-antitoxin (TA) systems are most commonly composed of two genes encoding a stable toxin, which harms the cell, and an unstable antitoxin that can inactivate it. TA systems were initially characterized as selfish elements, but have recently gained attention for regulating general stress responses responsible for pathogen virulence, formation of drug-tolerant persister cells and biofilms—all implicated in causing recalcitrant chronic infections. We use a bioinformatics approach to explore the distribution and evolution of type II TA loci of the opportunistic pathogen, Pseudomonas aeruginosa, across longitudinally sampled isolates from cystic fibrosis lungs. We identify their location in the genome, mutations, and gain/loss during infection to elucidate their function(s) in stabilizing selfish elements and pathogenesis. We found (1) 26 distinct TA systems, where all isolates harbor four in their core genome and a variable number of the remaining 22 on genomic islands; (2) limited mutations in core genome TA loci, suggesting they are not under negative selection; (3) no evidence for horizontal transmission of elements with TA systems between clone types within patients, despite their ability to mobilize; (4) no gain and limited loss of TA-bearing genomic islands, and of those elements partially lost, the remnant regions carry the TA systems supporting their role in genomic stabilization; (5) no significant correlation between frequency of TA systems and strain ability to establish as chronic infection, but those with a particular TA, are more successful in establishing a chronic infection.http://journal.frontiersin.org/article/10.3389/fmicb.2017.01180/fulltoxin-antitoxin systemPseudomonas aeruginosacystic fibrosisinfectionlongitudinal studieschronic infection |
| spellingShingle | Sandra B. Andersen Sandra B. Andersen Melanie Ghoul Ashleigh S. Griffin Bent Petersen Helle K. Johansen Søren Molin Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis Lungs Frontiers in Microbiology toxin-antitoxin system Pseudomonas aeruginosa cystic fibrosis infection longitudinal studies chronic infection |
| title | Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis Lungs |
| title_full | Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis Lungs |
| title_fullStr | Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis Lungs |
| title_full_unstemmed | Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis Lungs |
| title_short | Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis Lungs |
| title_sort | diversity prevalence and longitudinal occurrence of type ii toxin antitoxin systems of pseudomonas aeruginosa infecting cystic fibrosis lungs |
| topic | toxin-antitoxin system Pseudomonas aeruginosa cystic fibrosis infection longitudinal studies chronic infection |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2017.01180/full |
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