Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections
Abstract Acinetobacter baumannii is a clinical threat to human health, causing major infection outbreaks worldwide. As new drugs against Gram-negative bacteria do not seem to be forthcoming, and due to the microbial capability of acquiring multi-resistance, there is an urgent need for novel therapeu...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-03416-2 |
| _version_ | 1818835111277232128 |
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| author | Luana Presta Emanuele Bosi Leila Mansouri Lenie Dijkshoorn Renato Fani Marco Fondi |
| author_facet | Luana Presta Emanuele Bosi Leila Mansouri Lenie Dijkshoorn Renato Fani Marco Fondi |
| author_sort | Luana Presta |
| collection | DOAJ |
| description | Abstract Acinetobacter baumannii is a clinical threat to human health, causing major infection outbreaks worldwide. As new drugs against Gram-negative bacteria do not seem to be forthcoming, and due to the microbial capability of acquiring multi-resistance, there is an urgent need for novel therapeutic targets. Here we have derived a list of new potential targets by means of metabolic reconstruction and modelling of A. baumannii ATCC 19606. By integrating constraint-based modelling with gene expression data, we simulated microbial growth in normal and stressful conditions (i.e. following antibiotic exposure). This allowed us to describe the metabolic reprogramming that occurs in this bacterium when treated with colistin (the currently adopted last-line treatment) and identify a set of genes that are primary targets for developing new drugs against A. baumannii, including colistin-resistant strains. It can be anticipated that the metabolic model presented herein will represent a solid and reliable resource for the future treatment of A. baumannii infections. |
| first_indexed | 2024-12-19T02:45:31Z |
| format | Article |
| id | doaj.art-ad8bd12afc6c4b0f8a8764e490f98663 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T02:45:31Z |
| publishDate | 2017-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ad8bd12afc6c4b0f8a8764e490f986632022-12-21T20:38:54ZengNature PortfolioScientific Reports2045-23222017-06-017111210.1038/s41598-017-03416-2Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infectionsLuana Presta0Emanuele Bosi1Leila Mansouri2Lenie Dijkshoorn3Renato Fani4Marco Fondi5Department of Biology, University of FlorenceDepartment of Biology, University of FlorenceDepartment of Biology, University of FlorenceDepartment of Infectious Diseases, Leiden University Medical CenterDepartment of Biology, University of FlorenceDepartment of Biology, University of FlorenceAbstract Acinetobacter baumannii is a clinical threat to human health, causing major infection outbreaks worldwide. As new drugs against Gram-negative bacteria do not seem to be forthcoming, and due to the microbial capability of acquiring multi-resistance, there is an urgent need for novel therapeutic targets. Here we have derived a list of new potential targets by means of metabolic reconstruction and modelling of A. baumannii ATCC 19606. By integrating constraint-based modelling with gene expression data, we simulated microbial growth in normal and stressful conditions (i.e. following antibiotic exposure). This allowed us to describe the metabolic reprogramming that occurs in this bacterium when treated with colistin (the currently adopted last-line treatment) and identify a set of genes that are primary targets for developing new drugs against A. baumannii, including colistin-resistant strains. It can be anticipated that the metabolic model presented herein will represent a solid and reliable resource for the future treatment of A. baumannii infections.https://doi.org/10.1038/s41598-017-03416-2 |
| spellingShingle | Luana Presta Emanuele Bosi Leila Mansouri Lenie Dijkshoorn Renato Fani Marco Fondi Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections Scientific Reports |
| title | Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections |
| title_full | Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections |
| title_fullStr | Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections |
| title_full_unstemmed | Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections |
| title_short | Constraint-based modeling identifies new putative targets to fight colistin-resistant A. baumannii infections |
| title_sort | constraint based modeling identifies new putative targets to fight colistin resistant a baumannii infections |
| url | https://doi.org/10.1038/s41598-017-03416-2 |
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