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β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects
Pseudomonas aeruginosa is a major opportunistic pathogen, causing a wide range of acute and chronic infections. β-lactam antibiotics including penicillins, carbapenems, monobactams, and cephalosporins play a key role in the treatment of P. aeruginosa infections. However, a significant number of isol...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706265/ https://www.ncbi.nlm.nih.gov/pubmed/34959593 http://dx.doi.org/10.3390/pathogens10121638 |
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author | Glen, Karl A. Lamont, Iain L. |
author_facet | Glen, Karl A. Lamont, Iain L. |
author_sort | Glen, Karl A. |
collection | PubMed |
description | Pseudomonas aeruginosa is a major opportunistic pathogen, causing a wide range of acute and chronic infections. β-lactam antibiotics including penicillins, carbapenems, monobactams, and cephalosporins play a key role in the treatment of P. aeruginosa infections. However, a significant number of isolates of these bacteria are resistant to β-lactams, complicating treatment of infections and leading to worse outcomes for patients. In this review, we summarize studies demonstrating the health and economic impacts associated with β-lactam-resistant P. aeruginosa. We then describe how β-lactams bind to and inhibit P. aeruginosa penicillin-binding proteins that are required for synthesis and remodelling of peptidoglycan. Resistance to β-lactams is multifactorial and can involve changes to a key target protein, penicillin-binding protein 3, that is essential for cell division; reduced uptake or increased efflux of β-lactams; degradation of β-lactam antibiotics by increased expression or altered substrate specificity of an AmpC β-lactamase, or by the acquisition of β-lactamases through horizontal gene transfer; and changes to biofilm formation and metabolism. The current understanding of these mechanisms is discussed. Lastly, important knowledge gaps are identified, and possible strategies for enhancing the effectiveness of β-lactam antibiotics in treating P. aeruginosa infections are considered. |
format | Online Article Text |
id | pubmed-8706265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87062652021-12-25 β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects Glen, Karl A. Lamont, Iain L. Pathogens Review Pseudomonas aeruginosa is a major opportunistic pathogen, causing a wide range of acute and chronic infections. β-lactam antibiotics including penicillins, carbapenems, monobactams, and cephalosporins play a key role in the treatment of P. aeruginosa infections. However, a significant number of isolates of these bacteria are resistant to β-lactams, complicating treatment of infections and leading to worse outcomes for patients. In this review, we summarize studies demonstrating the health and economic impacts associated with β-lactam-resistant P. aeruginosa. We then describe how β-lactams bind to and inhibit P. aeruginosa penicillin-binding proteins that are required for synthesis and remodelling of peptidoglycan. Resistance to β-lactams is multifactorial and can involve changes to a key target protein, penicillin-binding protein 3, that is essential for cell division; reduced uptake or increased efflux of β-lactams; degradation of β-lactam antibiotics by increased expression or altered substrate specificity of an AmpC β-lactamase, or by the acquisition of β-lactamases through horizontal gene transfer; and changes to biofilm formation and metabolism. The current understanding of these mechanisms is discussed. Lastly, important knowledge gaps are identified, and possible strategies for enhancing the effectiveness of β-lactam antibiotics in treating P. aeruginosa infections are considered. MDPI 2021-12-18 /pmc/articles/PMC8706265/ /pubmed/34959593 http://dx.doi.org/10.3390/pathogens10121638 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Glen, Karl A. Lamont, Iain L. β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects |
title | β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects |
title_full | β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects |
title_fullStr | β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects |
title_full_unstemmed | β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects |
title_short | β-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects |
title_sort | β-lactam resistance in pseudomonas aeruginosa: current status, future prospects |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706265/ https://www.ncbi.nlm.nih.gov/pubmed/34959593 http://dx.doi.org/10.3390/pathogens10121638 |
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