β-lactam Resistance in <i>Pseudomonas aeruginosa</i>: Current Status, Future Prospects
<i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> infections....
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/10/12/1638 |
| _version_ | 1797501669438652416 |
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| author | Karl A. Glen Iain L. Lamont |
| author_facet | Karl A. Glen Iain L. Lamont |
| author_sort | Karl A. Glen |
| collection | DOAJ |
| description | <i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i>. We then describe how β-lactams bind to and inhibit <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> infections are considered. |
| first_indexed | 2024-03-10T03:21:52Z |
| format | Article |
| id | doaj.art-d3609037237a4de096375a9ca41f3c8f |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T03:21:52Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-d3609037237a4de096375a9ca41f3c8f2023-11-23T10:01:52ZengMDPI AGPathogens2076-08172021-12-011012163810.3390/pathogens10121638β-lactam Resistance in <i>Pseudomonas aeruginosa</i>: Current Status, Future ProspectsKarl A. Glen0Iain L. Lamont1Department of Biochemistry, University of Otago, P.O. Box 56, Dunedin 9054, New ZealandDepartment of Biochemistry, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand<i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i>. We then describe how β-lactams bind to and inhibit <i>P. aeruginosa</i> 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 <i>P. aeruginosa</i> infections are considered.https://www.mdpi.com/2076-0817/10/12/1638antibiotic resistancenosocomial infectioncystic fibrosiscarbapenemcephalosporinβ-lactamase |
| spellingShingle | Karl A. Glen Iain L. Lamont β-lactam Resistance in <i>Pseudomonas aeruginosa</i>: Current Status, Future Prospects Pathogens antibiotic resistance nosocomial infection cystic fibrosis carbapenem cephalosporin β-lactamase |
| title | β-lactam Resistance in <i>Pseudomonas aeruginosa</i>: Current Status, Future Prospects |
| title_full | β-lactam Resistance in <i>Pseudomonas aeruginosa</i>: Current Status, Future Prospects |
| title_fullStr | β-lactam Resistance in <i>Pseudomonas aeruginosa</i>: Current Status, Future Prospects |
| title_full_unstemmed | β-lactam Resistance in <i>Pseudomonas aeruginosa</i>: Current Status, Future Prospects |
| title_short | β-lactam Resistance in <i>Pseudomonas aeruginosa</i>: Current Status, Future Prospects |
| title_sort | β lactam resistance in i pseudomonas aeruginosa i current status future prospects |
| topic | antibiotic resistance nosocomial infection cystic fibrosis carbapenem cephalosporin β-lactamase |
| url | https://www.mdpi.com/2076-0817/10/12/1638 |
| work_keys_str_mv | AT karlaglen blactamresistanceinipseudomonasaeruginosaicurrentstatusfutureprospects AT iainllamont blactamresistanceinipseudomonasaeruginosaicurrentstatusfutureprospects |