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Molecular Docking and Phylogenetic Characterization of the AdeB Efflux Pump in Clinical Multidrug-Resistant Acinetobacter baumannii isolates Docking and Phylogenetic Characterization

Hawraa Natiq Kabroot AL-Fatlawy
Journal of Progressive Medical Sciences, Vol. 2 No. 6 (2026): sixth issue for second volume 2026
Published: 2026-08-31

Abstract

Background: Acinetobacter baumannii has emerged as a major multidrug-resistant pathogen in hospital settings, largely driven by efflux-mediated resistance mechanisms. Aim and objectives: This study integrated phenotypic, molecular sequencing, phylogenetic and computational approaches to evaluate the AdeB efflux pump as a potential therapeutic target in clinical Carbapenem-Resistant A. baumannii isolates (CRAB). Results: Among 354 clinical specimens collected from hospitalized adult patients in Najaf, Iraq, 47 A. baumannii isolates (13.3%) were identified and confirmed. Phenotypic susceptibility testing on all 47 isolates revealed high resistance rates across multiple antibiotic classes, including complete resistance to imipenem, gentamicin and amikacin (100%), as well as high resistance to cefepime (93.6%), meropenem (91.5%), and ciprofloxacin (82.9%). Overall, 43 isolates (91.5%) were classified as phenotypic carbapenem-resistant A. baumannii (CRAB), and 41 isolates (87.2%) were categorized as multidrug-resistant (MDR). A selected subset of 39 high-level CRAB isolates was subjected to molecular PCR analysis, revealing universal detection of the AdeB efflux pump gene (100%), alongside a widespread distribution of key resistance determinants including blaOXA-51, blaOXA-23, IMP, Class 1 integrons, and ESBL genes (blaCTX, blaTEM, and blaSHV). Sequencing and phylogenetic analysis of AdeB and gyrB genes demonstrated high sequence conservation and close evolutionary relatedness to global reference strains. The partial Adeb gene sequence generated in this study was deposited in the DNA Data Bank of Japan (DDBJ) under accession number LC918549. Three-dimensional structural modelling of the AdeB showed excellent stereochemical quality, with 98.71% of residues located in Ramachandran favoured regions. Normal mode analysis confirmed flexibility and functional stability. Conclusions: Molecular docking identified strong binding affinities of efflux pump inhibitors, with Paβn showing the highest affinity (-9.1 kcal/mol) followed by the Pyridopyrimidine derivative (–8.3 kcal/mol). Molecular dynamics simulations further validated the structural stability of AdeB, particularly at the 25 ns. Collectively, these finding support AdeB as a stable druggable target and highlight efflux pump inhibition as a promising strategy against multidrug-resistant A. baumannii.


 

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Hawraa Natiq Kabroot AL-Fatlawy
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