β-lactam Resistance in Pseudomonas aeruginosa : Current Status, Future Prospects.
Karl A GlenIain L LamontPublished in: Pathogens (Basel, Switzerland) (2021)
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.
Keyphrases
- pseudomonas aeruginosa
- biofilm formation
- current status
- gram negative
- binding protein
- cystic fibrosis
- healthcare
- candida albicans
- staphylococcus aureus
- escherichia coli
- end stage renal disease
- multidrug resistant
- randomized controlled trial
- acinetobacter baumannii
- chronic kidney disease
- newly diagnosed
- systematic review
- liver failure
- stem cells
- public health
- drug resistant
- prognostic factors
- poor prognosis
- genome wide
- type diabetes
- gene expression
- single cell
- dna methylation
- intensive care unit
- transcription factor
- small molecule
- patient reported outcomes
- mesenchymal stem cells
- acute respiratory distress syndrome
- amino acid
- protein protein
- genome wide identification
- bacillus subtilis