Synthetic aminoglycoside derivatives as anti-virulence agents against multidrug-resistant Acinetobacter baumannii
A systematic review
Keywords:
AbaR, Acinetobacter baumannii, aminoglycoside derivatives, BfmR, biofilm inhibition, molecular docking, quorum sensingAbstract
Acinetobacter baumannii presents a severe clinical challenge in critical care due to its rapid acquisition of drug resistance and its ability to form dense biofilms on medical equipment. While traditional antibiotic research focuses almost exclusively on essential bacterial viability targets, targeting virulence factors at sub-inhibitory concentrations (sub-MIC) offers an alternative approach to reduce pathogen persistence without driving immediate resistance. This systematic review synthesizes the literature published between January 2010 and July 2026 that evaluates chemically modified aminoglycoside derivatives designed to bypass aminoglycoside-modifying enzymes (AMEs) and impair A. baumannii virulence pathways. Evidence from the included studies indicates that targeted modifications to the 2-deoxystreptamine core, specifically inserting hydrophobic or amphiphilic side chains, restore susceptibility in carbapenem-resistant A. baumannii (CRAB) strains. Furthermore, these derivatives significantly reduce biofilm biomass (often by over 80% at 21×MIC) and restrict surface twitching motility. Computational docking models across these studies point to multi-target engagement, where modified derivatives interact directly with outer membrane protein A (OmpA), the quorum-sensing receptor AbaR, and the response regulator BfmR. Rational scaffold engineering of aminoglycosides offers a viable approach to develop dual-action agents that combine direct antibacterial activity with phenotypic disarming.
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References
- Elanany, A. A. (2025). Antivirulence drugs against Acinetobacter baumannii: where do they stand? World Journal of Microbiology and Biotechnology, 41(1), Article 41165876.
- Kim, H.-J., Kim, N.-Y., Ko, S.-Y., Park, S.-Y., Oh, M.-H., Shin, M.-S., Lee, Y.-C., & Lee, J.-C. (2022). Complementary regulation of BfmRS two-component and AbaIR quorum sensing systems to express virulence-associated genes in Acinetobacter baumannii. International Journal of Molecular Sciences, 23(21), 13136. https://doi.org/10.3390/ijms232113136
- Ramirez, M. S., & Tolmasky, M. E. (2010). Aminoglycoside modifying enzymes. Drug Resistance Updates, 13(6), 151–171. https://doi.org/10.1016/j.drup.2010.08.0034
- Sati, H. (2025). The WHO bacterial priority pathogens list 2024: A prioritisation study to guide research, development, and public health strategies against antimicrobial resistance. The Lancet Infectious Diseases, 25(4), 40245910.
- Tapia-Rodriguez, M. R., Cantu-Soto, E. U., Vazquez-Armenta, F. J., Bernal-Mercado, A. T., & Ayala-Zavala, J. F. (2023). Inhibition of Acinetobacter baumannii biofilm formation by terpenes from oregano (Lippia graveolens) essential oil. Antibiotics, 12(10), 1539. https://doi.org/10.3390/antibiotics12101539
- Peleg, A. Y., Seifert, H., & Paterson, D. L. (2008). Acinetobacter baumannii: emergence of a successful pathogen. Clinical Microbiology Reviews, 21(3), 538–582.
- Imperi, F., et al. (2014). New strategies to tackle antibiotic resistance: the anti-virulence approach. Current Opinion in Microbiology, 18, 52–57.
- Tomaras, A. P., et al. (2003). Attachment to and biofilm formation on a polystyrene surface by Acinetobacter baumannii involves pilus production. Microbiology, 149(12), 3473–3484.
- Gao, W., et al. (2020). Structural basis of quorum sensing inhibition in Acinetobacter baumannii. ACS Infectious Diseases, 6(8), 2105–2114.
- Eijkelkamp, B. A., et al. (2014). Sex and motility in Acinetobacter baumannii. Frontiers in Microbiology, 5, 233.
- Tang, K., Zhang, X., & Ni, B. (2021). Quorum sensing inhibition or quenching in Acinetobacter baumannii: The novel therapeutic strategies for new drug development. Frontiers in Microbiology, 12, 558003.
- Flores-Contreras, E. A., et al. (2023). Inhibition of Acinetobacter baumannii biofilm formation by terpenes from Lippia graveolens essential oil. Antibiotics, 12(10), 1539.
- Mladenović, K. G., et al. (2022). Cinnamon essential oil and its emulsion as efficient antibiofilm agents to combat Acinetobacter baumannii. Frontiers in Microbiology, 13, 989667.
- Mladenović, K. G., et al. (2020). Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathoge, ; doi:10.3390/antibiotics9030119
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