Phytochemical inhibition of quorum sensing and biofilm formation by Paederia foetida Linn. against multidrug-resistant Acinetobacter baumannii: An integrated in vitro and in silico investigation

Vet World Vol.18 August-2025 Article - 3

Research Article

Veterinary World, 18(8): 2181-2193

https://doi.org/10.14202/vetworld.2025.2181-2193

Sirijan Santajit^1,2, Techit Thavorasak³, Dararat Horpet¹, Thida Kong-ngoen³, Uttapol Permpoon⁴, Chul Young Kim⁴, Tae-Gyu Nam⁴, and Nitaya Indrawattana^5,6,7

1. Department of Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala, 80160, Thailand.

2. Center of Excellence in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat, 80160, Thailand.

3. Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand.

4. Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University ERICA, Ansan, Gyeonggi-do, 15588, Republic of Korea.

5. Biomedical Research Incubator Unit, Department of Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.

6. Siriraj Center of Research Excellence in Allergy and Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.

7. Biodesign Innovation Program, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.

Background and Aim: Acinetobacter baumannii is a multidrug-resistant (MDR) pathogen notorious for its biofilm formation and persistence in clinical and veterinary settings. Its resistance is exacerbated by quorum sensing (QS) pathways that regulate virulence and biofilm maturation. Disrupting QS and biofilm integrity using plant-derived compounds presents a promising alternative to traditional antibiotics. This study aimed to evaluate the antibiofilm and anti-QS potential of Paederia foetida Linn. ethanolic extract against A. baumannii, integrating gas chromatography–mass spectrometry (GC-MS) profiling, molecular docking, and in vitro assays.

Materials and Methods: Leaves of P. foetida were extracted with ethanol and analyzed by GC-MS to identify major bioactive constituents. Molecular docking was conducted against five QS and biofilm-associated A. baumannii proteins (AF-A0A7S8WE28-F1-v4, AF-A0A059ZL64-F1-v4, AF-Q2VSW6-F1-v4, AF-A0A2P1B9S4-F1-v4, and AF-A0A5P9VY74-F1-v4). Absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles and drug-likeness of key compounds were assessed in silico. Antimicrobial activity was determined by broth microdilution (minimum inhibitory concentration [MIC]/minimum bactericidal concentration [MBC]), and biofilm inhibition was evaluated through crystal violet microtiter assays. Morphological damage was examined using field emission scanning electron microscopy (FE-SEM).

Results: GC-MS identified 30 phytoconstituents, with 5-hydroxymethyl-2-furaldehyde, 4H-pyran-4-one derivative, and eugenol as predominant compounds. Eugenol exhibited the highest binding affinity, particularly with AbaR (−6.3 kcal/mol). The extract showed significant antimicrobial activity (MIC = 7.81 mg/mL; MBC = 31.25 mg/mL) and dose-dependent inhibition of biofilm biomass (p < 0.001). FE-SEM imaging confirmed dose-responsive membrane damage and disruption of the biofilm. ADMET predictions revealed favorable oral bioavailability and low toxicity for selected compounds.

Conclusion: P. foetida extract exhibits potent antibacterial, anti-QS, and antibiofilm activity against MDR A. baumannii, supported by its phytochemical diversity, favorable pharmacokinetics, and strong protein-ligand interactions. These findings suggest its promise as a plant-derived therapeutic aligned with the One Health framework to combat antimicrobial resistance in both human and veterinary medicine.

Keywords: Acinetobacter baumannii, absorption, distribution, metabolism, excretion, and toxicity, biofilm disruption, eugenol, gas chromatography–mass spectrometry, molecular docking, One Health, Paederia foetida, quorum sensing inhibition.

How to cite this article: Santajit S, Thavorasak T, Horpet D, Kong-ngoen T, Permpoon U, Kim CY, Nam T, and Indrawattana N (2025) Phytochemical inhibition of quorum sensing and biofilm formation by Paederia foetida Linn. against multidrug-resistant Acinetobacter baumannii: An integrated in vitro and in silico investigation, Veterinary World, 18(8): 2181-2193.

Received: 01-04-2025 Accepted: 08-07-2025 Published online: 02-08-2025

Corresponding author: Nitaya Indrawattana E-mail: nitaya.ind@mahidol.ac.th

DOI: 10.14202/vetworld.2025.2181-2193

Copyright: Santajit, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.