Carbapenem Resistance in Acinetobacter baumannii: Mechanisms, Therapeutics, and Innovations
Abstract
1. Emergence of Carbapenem-Resistant A. baumannii (CRAB)
2. Molecular Mechanisms of Carbapenem Resistance in A. baumannii
2.1. Beta-Lactamases
2.1.1. Class A Beta-Lactamases, Including Extended-Spectrum Beta-Lactamases (ESBLs)
Ambler Molecular and Structural Classification | Gene Family | Accession * | e.g., Genes | References |
---|---|---|---|---|
A | CTX-M beta-lactamase | ARO:3000016 | CTX-M-33 | [35,36] |
A | KPC beta-lactamase | ARO:3000059 | KPC-2 | [31,32] |
A | PER beta-lactamase | ARO:3000056 | PER-1 | [27,28] |
A | SHV beta-lactamase *** | ARO:3000015 | SHV-12 | [33,34,37] |
A | TEM beta-lactamase ** | ARO:3000014 | TEM-1 | [34] |
A | VEB beta-lactamase | ARO:3000043 | VEB-1 | [38,39] |
B or MBLs | GIM beta-lactamase | ARO:3003195 | GIM | [40] |
B or MBLs | IMP beta-lactamase | ARO:3000020 | IMP-1, IMP-11, IMP-2, IMP-4, IMP-5, IMP-6, IMP-69 | [41,42,43,44,45,46,47,48] |
B or MBLs | NDM beta-lactamase | ARO:3000057 | NDM-1, NDM-2 | [49] |
B or MBLs | SIM beta-lactamase | ARO:3004206 | SIM-1 | [41] |
B or MBLs | SPM beta-lactamase | ARO:3000580 | SPM | [50] |
B or MBLs | TMB beta-lactamase | ARO:3004104 | TMB-2 | [51] |
B or MBLs | VIM beta-lactamase | ARO:3000021 | VIM-2 | [52] |
C or para Cephalosporins | ADC beta-lactamase with carbapenemase activity | ARO:3004545 | ADC-68 *** | [53] |
2.1.2. Class B Beta-Lactamases or MBLs
2.1.3. Class C Beta-Lactamases
Gene Family | Variantes * | Accession ** | Associated Insertion Sequence Elements | Plasmid or Chromosomal | References |
---|---|---|---|---|---|
OXA-23-like beta-lactamase | 52 | ARO:3007710 | ISAba1 and ISAba4 | Chromosomal or Plasmid | [60] |
OXA-24-like beta-lactamase (or OXA-40-like beta-lactamase) | 14 | ARO:3007711 | ISAba1 | Chromosomal or Plasmid | [61] |
OXA-48-like beta-lactamase | 67 | ARO:3007721 | ND | ND | [62,63,64] |
OXA-51-like beta-lactamase | 383 | ARO:3007725 | ISAba1, ISAba2, ISAba825, ISAba15, ISAba16, ISAba19 | Chromosomal | [60,65] |
OXA-58-like beta-lactamase | 8 | ARO:3007728 | ISAba1, ISAba2, ISAba3, ISAba125 and IS18 | Chromosomal or Plasmid | [65,66] |
OXA-134-like beta-lactamase | 28 | ARO:3007700 | ND | ND | [62,65] |
OXA-143-like beta-lactamase | 11 | ARO:3007701 | ND | Plasmid | [11,62] |
2.1.4. Class D Beta-Lactamases or OXA-Type
2.1.5. Other Gene Families
2.2. Target Modifications and Reduced Antibiotic Access
2.2.1. Low Permeability of Its Outer Membrane (OM)
2.2.2. Altered Molecular Antibiotic Targets
2.2.3. Efflux Pumps
3. Promising Therapeutic Innovations Against CRAB
3.1. New Antibiotics
3.2. Combination Therapies
3.2.1. Sulbactam–Durlobactam
3.2.2. Ceftolozane–Tazobactam
3.2.3. Synergistic Use of Polymyxinswith Tetracyclines or Glycopeptides
3.2.4. Efficacy and Challenges of Combination Therapies in Resistant Strains
3.3. Development of New Carbapenemase Inhibitors
3.4. Alternative and Innovative Therapies
3.4.1. Development of New Efflux Pump Inhibitors
3.4.2. Phage Therapy
3.4.3. Antimicrobial Peptides (AMPs)
3.4.4. Gene Editing Tools
3.4.5. Nanoparticle-Based Strategies
4. Computational Approaches Supporting the Fight Against Carbapenem-Resistant A. baumannii
4.1. AI-Based Screening and Design of Antimicrobials
4.2. AI for Genomic Interpretation and Phenotype Prediction
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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de Souza, J.; D’Espindula, H.R.S.; Ribeiro, I.d.F.; Gonçalves, G.A.; Pillonetto, M.; Faoro, H. Carbapenem Resistance in Acinetobacter baumannii: Mechanisms, Therapeutics, and Innovations. Microorganisms 2025, 13, 1501. https://doi.org/10.3390/microorganisms13071501
de Souza J, D’Espindula HRS, Ribeiro IdF, Gonçalves GA, Pillonetto M, Faoro H. Carbapenem Resistance in Acinetobacter baumannii: Mechanisms, Therapeutics, and Innovations. Microorganisms. 2025; 13(7):1501. https://doi.org/10.3390/microorganisms13071501
Chicago/Turabian Stylede Souza, Joyce, Helena Regina Salomé D’Espindula, Isabel de Farias Ribeiro, Geiziane Aparecida Gonçalves, Marcelo Pillonetto, and Helisson Faoro. 2025. "Carbapenem Resistance in Acinetobacter baumannii: Mechanisms, Therapeutics, and Innovations" Microorganisms 13, no. 7: 1501. https://doi.org/10.3390/microorganisms13071501
APA Stylede Souza, J., D’Espindula, H. R. S., Ribeiro, I. d. F., Gonçalves, G. A., Pillonetto, M., & Faoro, H. (2025). Carbapenem Resistance in Acinetobacter baumannii: Mechanisms, Therapeutics, and Innovations. Microorganisms, 13(7), 1501. https://doi.org/10.3390/microorganisms13071501