Defining the core essential genome of Pseudomonas aeruginosa
© 2019 National Academy of Sciences. All rights reserved. Genomics offered the promise of transforming antibiotic discovery by revealing many new essential genes as good targets, but the results fell short of the promise. While numerous factors contributed to the disappointing yield, one factor was...
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2020
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| Online Access: | https://hdl.handle.net/1721.1/125218 |
| _version_ | 1811080963911843840 |
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| author | Lander, Eric S. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lander, Eric S. |
| author_sort | Lander, Eric S. |
| collection | MIT |
| description | © 2019 National Academy of Sciences. All rights reserved. Genomics offered the promise of transforming antibiotic discovery by revealing many new essential genes as good targets, but the results fell short of the promise. While numerous factors contributed to the disappointing yield, one factor was that essential genes for a bacterial species were often defined based on a single or limited number of strains grown under a single or limited number of in vitro laboratory conditions. In fact, the essentiality of a gene can depend on both the genetic background and growth condition. We thus developed a strategy for more rigorously defining the core essential genome of a bacterial species by studying many pathogen strains and growth conditions. We assessed how many strains must be examined to converge on a set of core essential genes for a species. We used transposon insertion sequencing (Tn-Seq) to define essential genes in nine strains of Pseudomonas aeruginosa on five different media and developed a statistical model, FiTnEss, to classify genes as essential versus nonessential across all strain–medium combinations. We defined a set of 321 core essential genes, representing 6.6% of the genome. We determined that analysis of four strains was typically sufficient in P. aeruginosa to converge on a set of core essential genes likely to be essential across the species across a wide range of conditions relevant to in vivo infection, and thus to represent attractive targets for novel drug discovery. |
| first_indexed | 2024-09-23T11:39:38Z |
| format | Article |
| id | mit-1721.1/125218 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:39:38Z |
| publishDate | 2020 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1252182022-10-01T05:07:21Z Defining the core essential genome of Pseudomonas aeruginosa Lander, Eric S. Massachusetts Institute of Technology. Department of Biology © 2019 National Academy of Sciences. All rights reserved. Genomics offered the promise of transforming antibiotic discovery by revealing many new essential genes as good targets, but the results fell short of the promise. While numerous factors contributed to the disappointing yield, one factor was that essential genes for a bacterial species were often defined based on a single or limited number of strains grown under a single or limited number of in vitro laboratory conditions. In fact, the essentiality of a gene can depend on both the genetic background and growth condition. We thus developed a strategy for more rigorously defining the core essential genome of a bacterial species by studying many pathogen strains and growth conditions. We assessed how many strains must be examined to converge on a set of core essential genes for a species. We used transposon insertion sequencing (Tn-Seq) to define essential genes in nine strains of Pseudomonas aeruginosa on five different media and developed a statistical model, FiTnEss, to classify genes as essential versus nonessential across all strain–medium combinations. We defined a set of 321 core essential genes, representing 6.6% of the genome. We determined that analysis of four strains was typically sufficient in P. aeruginosa to converge on a set of core essential genes likely to be essential across the species across a wide range of conditions relevant to in vivo infection, and thus to represent attractive targets for novel drug discovery. 2020-05-13T17:51:56Z 2020-05-13T17:51:56Z 2019-05 2020-01-22T18:55:24Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 https://hdl.handle.net/1721.1/125218 Lander, Eric S. 2019. "Defining the core essential genome of Pseudomonas aeruginosa." Proceedings of the National Academy of Sciences of the United States of America, 116 (20). en 10.1073/PNAS.1900570116 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Lander, Eric S. Defining the core essential genome of Pseudomonas aeruginosa |
| title | Defining the core essential genome of Pseudomonas aeruginosa |
| title_full | Defining the core essential genome of Pseudomonas aeruginosa |
| title_fullStr | Defining the core essential genome of Pseudomonas aeruginosa |
| title_full_unstemmed | Defining the core essential genome of Pseudomonas aeruginosa |
| title_short | Defining the core essential genome of Pseudomonas aeruginosa |
| title_sort | defining the core essential genome of pseudomonas aeruginosa |
| url | https://hdl.handle.net/1721.1/125218 |
| work_keys_str_mv | AT landererics definingthecoreessentialgenomeofpseudomonasaeruginosa |