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Acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by Pseudomonas aeruginosa via ICE(Tn4371)6385
Pseudomonas aeruginosa can cause life-threatening infections in immunocompromised patients. The first-line agents to treat P. aeruginosa infections are carbapenems. However, the emergence of carbapenem-resistant P. aeruginosa strains greatly compromised the effectiveness of carbapenem treatment, whi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123621/ https://www.ncbi.nlm.nih.gov/pubmed/30271939 http://dx.doi.org/10.1038/s42003-018-0064-0 |
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author | Ding, Yichen Teo, Jeanette W. P. Drautz-Moses, Daniela I. Schuster, Stephan C. Givskov, Michael Yang, Liang |
author_facet | Ding, Yichen Teo, Jeanette W. P. Drautz-Moses, Daniela I. Schuster, Stephan C. Givskov, Michael Yang, Liang |
author_sort | Ding, Yichen |
collection | PubMed |
description | Pseudomonas aeruginosa can cause life-threatening infections in immunocompromised patients. The first-line agents to treat P. aeruginosa infections are carbapenems. However, the emergence of carbapenem-resistant P. aeruginosa strains greatly compromised the effectiveness of carbapenem treatment, which makes the surveillance on their spreading and transmission important. Here we characterized the full-length genomes of two carbapenem-resistant P. aeruginosa clinical isolates that are capable of producing New Delhi metallo-β-lactamase-1 (NDM-1). We show that bla(NDM-1) is carried by a novel integrative and conjugative element (ICE) ICE(Tn4371)6385, which also carries the macrolide resistance gene msr(E) and the florfenicol resistance gene floR. By exogenously expressing msr(E) in P. aeruginosa laboratory strains, we show that Msr(E) can abolish azithromycin-mediated quorum sensing inhibition in vitro and anti-Pseudomonas effect in vivo. We conclude that ICEs are important in transmitting carbapenem resistance, and that anti-virulence treatment of P. aeruginosa infections using sub-inhibitory concentrations of macrolides can be challenged by horizontal gene transfer. |
format | Online Article Text |
id | pubmed-6123621 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61236212018-09-28 Acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by Pseudomonas aeruginosa via ICE(Tn4371)6385 Ding, Yichen Teo, Jeanette W. P. Drautz-Moses, Daniela I. Schuster, Stephan C. Givskov, Michael Yang, Liang Commun Biol Article Pseudomonas aeruginosa can cause life-threatening infections in immunocompromised patients. The first-line agents to treat P. aeruginosa infections are carbapenems. However, the emergence of carbapenem-resistant P. aeruginosa strains greatly compromised the effectiveness of carbapenem treatment, which makes the surveillance on their spreading and transmission important. Here we characterized the full-length genomes of two carbapenem-resistant P. aeruginosa clinical isolates that are capable of producing New Delhi metallo-β-lactamase-1 (NDM-1). We show that bla(NDM-1) is carried by a novel integrative and conjugative element (ICE) ICE(Tn4371)6385, which also carries the macrolide resistance gene msr(E) and the florfenicol resistance gene floR. By exogenously expressing msr(E) in P. aeruginosa laboratory strains, we show that Msr(E) can abolish azithromycin-mediated quorum sensing inhibition in vitro and anti-Pseudomonas effect in vivo. We conclude that ICEs are important in transmitting carbapenem resistance, and that anti-virulence treatment of P. aeruginosa infections using sub-inhibitory concentrations of macrolides can be challenged by horizontal gene transfer. Nature Publishing Group UK 2018-05-31 /pmc/articles/PMC6123621/ /pubmed/30271939 http://dx.doi.org/10.1038/s42003-018-0064-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ding, Yichen Teo, Jeanette W. P. Drautz-Moses, Daniela I. Schuster, Stephan C. Givskov, Michael Yang, Liang Acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by Pseudomonas aeruginosa via ICE(Tn4371)6385 |
title | Acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by Pseudomonas aeruginosa via ICE(Tn4371)6385 |
title_full | Acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by Pseudomonas aeruginosa via ICE(Tn4371)6385 |
title_fullStr | Acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by Pseudomonas aeruginosa via ICE(Tn4371)6385 |
title_full_unstemmed | Acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by Pseudomonas aeruginosa via ICE(Tn4371)6385 |
title_short | Acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by Pseudomonas aeruginosa via ICE(Tn4371)6385 |
title_sort | acquisition of resistance to carbapenem and macrolide-mediated quorum sensing inhibition by pseudomonas aeruginosa via ice(tn4371)6385 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123621/ https://www.ncbi.nlm.nih.gov/pubmed/30271939 http://dx.doi.org/10.1038/s42003-018-0064-0 |
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