Myrtenol Inhibits Biofilm Formation and Virulence in the Drug-Resistant Acinetobacter baumannii: Insights into the Molecular Mechanisms

Lei Liu; Bin Liu; Liang Li; Ming-Xin He; Xiang-Dong Zhou; Qi Li

doi:10.2147/IDR.S379212

Myrtenol Inhibits Biofilm Formation and Virulence in the Drug-Resistant Acinetobacter baumannii: Insights into the Molecular Mechanisms

Infect Drug Resist. 2022 Sep 2:15:5137-5148. doi: 10.2147/IDR.S379212. eCollection 2022.

Authors

Lei Liu^#^{1

2}, Bin Liu^#^{1

2}, Liang Li^{1

2}, Ming-Xin He², Xiang-Dong Zhou^{1

2}, Qi Li^{1

2}

Affiliations

¹ Department of Respiratory Medicine, the First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People's Republic of China.
² NHC Key Laboratory of Tropical Disease Control, Hainan Medical University, Haikou, Hainan, People's Republic of China.

^# Contributed equally.

Abstract

Background: blaNDM-1-producing Acinetobacter baumannii (BP-AB) remains a critical problem in nosocomial infections, because of its resistance mediated by the biofilm formation and virulence factors. No studies have confirmed myrtenol's efficacy in inhibiting the biofilm formation and virulence associated with biofilm of BP-AB.

Methods: The tested concentrations of myrtenol were wild type (A), 50 μg/mL (B), 100 μg/mL (C), 200 μg/mL (D), 250 μg/mL (E), and 300 μg/mL (F).

Results: The BP-AB biofilm inhibition was significantly higher in the D, E, and F groups than in the A, B, and C groups. Myrtenol significantly reduced the air-liquid interface ring formation in glass tubes. It also effectively inhibited the attachment of BP-AB strains on polystyrene surfaces as shown by crystal violet staining. Microscopy showed a significant reduction in biofilm formation with dispersed BP-AB strains. The confocal laser scanning microscopy analysis showed a significant reduction in the biofilm's biomass, covered surface area, and thickness. The scanning electron microscopy analysis revealed significantly fewer BP-AB aggregates on the coverslip surface. In the CompStat analysis, the biofilm's biomass, maximum thickness, and surface-to-volume ratio were significantly reduced. The qPCR analysis revealed a significant down-regulation of bfmR, bap, csuA/B, and ompA expression, which positively correlated with the biofilm's biomass, maximum thickness, and surface-to-volume ratio in BP-AB strains. Myrtenol significantly improved the susceptibility of BP-AB to the antibiotics amikacin, piperacillin/tazobactam, cefoperazone/sulbactam, and ceftazidime.

Conclusion: Myrtenol attenuates the BP-AB biofilm formation and virulence by suppressing the expression of bfmR, bap, csuA/B, and ompA.

Keywords: Acinetobacter baumannii; biofilm; myrtenol; resistance; virulence factors.

Grants and funding

The present study was supported by Hainan Provincial Natural Science Foundation of China, project number:822MS176. The project supported by the Education Department of Hainan Province, project number: Hnky2022ZD-11. This study was supported by the Open Foundation of NHC Key Laboratory of Tropical Disease Control, Hainan Medical University (2021NHCTDCKFKT21008), the project supported by Hainan Province Clinical Medical Center.