In Silico Docking, Resistance Modulation and Biofilm Gene Expression in Multidrug-Resistant Acinetobacter baumannii via Cinnamic and Gallic Acids

Abstract

Despite the mounting global burden of antimicrobial resistance (AMR), the generation of new classes of effective antimicrobials still lags far behind. The interplay between multidrug resistance and biofilm formation in Acinetobacter baumannii has drastically narrowed the available therapeutic choices. The use of natural compounds holds promise as an alternate option for restoring the activity of existing antibiotics and attenuating virulence traits through reduced biofilm formation. This study aimed to evaluate the modulatory effect of combining cinnamic and gallic acids at ½MIC with various antibiotics against multidrug-resistant (MDR) A. baumannii clinical isolates as well as study the effect on the expression of the biofilm-associated genes (bap, csuE, ompA) via quantitative, real-time PCR. Combining cinnamic or gallic acid with imipenem, amikacin or doxycycline resulted in significant reduction of resistance (p < 0.05). On the contrary, no effect was recorded when both acids were combined with levofloxacin, and only cinnamic acid had a synergistic effect with colistin. The transcriptomic changes of biofilm-related genes in the presence of gallic acid at ½MIC were compared with untreated control samples. The fold expression values proved that gallic acid substantially down-regulated the respective genes in all five strong biofilm formers. Molecular docking studies of gallic and cinnamic acids on target genes revealed good binding affinities and verified the proposed mechanism of action. To the best of our knowledge, this is the first report on the effect of gallic acid on the expression of bap, csuE and ompA genes in A. baumannii, which may permit its use as an adjunct anti-virulence therapeutic strategy.

Antibacterial and antibiofilm potentials of Rumex dentatus root extract characterized by HPLC-ESI-Q-TOF-MS

“…Gallic acid has been documented to exhibit lower binding energies in previous studies, albeit with a different target protein. Nevertheless, these findings confirm the antibacterial potential of gallic acid through molecular docking analysis ( Abdelaziz et al, 2022 ). Similarly, previous studies have confirmed that emodin also possesses the potential to inhibit bacterial growth ( Ding et al, 2011 ).…”

Modulating the transcriptomic profile of multidrug-resistant Klebsiella pneumoniae biofilm formation by antibiotics in combination with zinc sulfate

“…Plates were treated with zinc (0.25 MIC) and tested antibiotics (0.5 MBIC) alone and in combinations. The bacterial growth was evaluated turbidimetrically in independent triplicates by measuring the OD600 using ELx800, Biotek (Winooski, VT, USA) at 2, 4, 6, 18, 20 and 24 h time intervals and compared to the control wells [ 16 ].…”

Novel Coumarins Derivatives for A. baumannii Lung Infection Developed by High-Throughput Screening and Reinforcement Learning

“…The reinforcement learning approach that was implemented and performed in the current study is based on the widely used molecule deep Q-networks (MolDQN) (Zhou et al 2019). During the reinforcement learning process, a known molecule that has been proved to have excellent bioactivities depending on demands and requirements of the study (in the current work, the desired molecule is the inhibitor of A. baumannii) is used as the training template (Almihyawi et al 2022;Abdelaziz et al 2022). Then, multiple actions are allowed to modify the template and generate novel structure which is expected to have similar or even better bioactivity than the given template, the allowed actions are atom addition, bond addition, bond removal and un-modification.…”

“…Recently, the coumarins exhibit a plethora of biological activities, such as anti-inflammatory and anti-tumor effect. In 2016, Jyoti Dandriyal has revealed that the C-4 substituted coumarin derivatives showed excellent anti-cancer activity (Abdelaziz et al 2022). The Yang Hu revealed the also showed coumarin derivatives were considered as a promising lead compound for the development of commercial drugs (Hu et al 2019).…”