همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Potential of Lavender extract to inhibit efflux pump AdeB in multidrug resistant of Acinetobacter baumnii

نویسندگان :

Masoumeh Shakarami¹ Behzad Shahbazi² Ladan Mafakher³

1- Student Research Committee, Maragheh University of Medical Science, Maragheh, Iran 2- School of Pharmacy, Semnan University of Medical Sciences, Semnan, Iran;c Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran 3- Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

کلمات کلیدی :

AdeABC pump،Acinetobacter baumannii،Lavender،Molecular docking

چکیده :

Introduction: Acinetobacter baumannii is one of the six most dangerous multidrug-resistant pathogens in hospitals across the globe which estimated 10% of hospital-acquired infections are thought to be caused by this bacterium. Currently, up to 43% of clinical isolates of A. baumannii have become resistant to at least three different antibiotic classes (CastanheiraMendes and Gales, 2023)Efflux pumps, particularly those belonging to the resistance-nodulation-division (RND) superfamily, significantly contribute to MDR in Gram-negative bacteria. The AdeABC efflux pump is a key player in A. baumannii antibiotic resistance, comprising AdeB (an RND transporter), AdeA (a periplasmic membrane fusion protein), and AdeC (an outer membrane factor protein)(Leus et al., 2024). Given the reported antimicrobial activity of lavender's chemical constituents(Denkova et al., 2023). This study investigated the potential of lavender compounds to inhibit the AdeABC pump in A. baumannii. Material and Methods: Lavender's chemical composition was identified through a literature review. Compound structures were obtained from PubChem (https://pubchem.ncbi.nlm.nih.gov/). The AdeABC pump structure was retrieved from the Protein Data Bank (PDB ID: 7KGF). Molecular docking was performed using Autodock Vina (https://vina.scripps.edu/). Compounds exhibiting the highest binding affinity to the AdeABC binding site were selected for further analysis using Ligplot package. The Pain Remover web server was applied to exclude compounds with poor properties that could'nt be used as drug candidates(https://www.cbligand.org/PAINS/). Lipinski's rule of five and safety assessment were applied using DataWarrior software to evaluate the physicochemical properties of the top-scoring compounds (https://openmolecules.org/datawarrior/). Result and Discussion: Docking analysis revealed three distinct potential binding sites on the AdeABC pump. Carvone, caryophyllene, cumin aldehyde, γ-terpinene, and terpinene-4-ol demonstrated strong binding affinities (approximately -6 kcal/mol) to all three sites. LigPlot analysis confirmed effective interactions with key residues within the binding sites of AdeABC pump. PainRemover indicated that all five compounds possessed favorable drug-like properties. According to Lipinski's rule of five, two compounds met the criteria. Finally, a safety assessment indicated that one of these two compounds showed low potential for mutagenesis, tumorigenicity, irritation, and reproductive toxicity.This aligns with Leus et al. (2024), who demonstrated that compounds interacting with key AdeABC residues can effectively inhibit efflux pump activity in Acinetobacter baumannii. Conclusion: Our findings suggest that among Lavender compounds, terpinene-4-ol possesses significant potential as an antimicrobial agent against MDR A. baumannii through AdeABC pump inhibition. Further investigation is warranted to validate these in silico findings through experimental studies.