After almost 100 years since evidence of biofilm mode of growth and decades of intensive investigation about their formation, regulatory pathways and mechanisms of antimicrobial tolerance, nowadays there are still no therapeutic solutions to eradicate bacterial biofilms and their biomedical related issues. This review intends to provide a comprehensive summary of the recent and most relevant published studies on plant-based products, or their isolated compounds with antibiofilm activity mechanisms of action or identified molecular targets against bacterial biofilms. The objective is to offer a new perspective of most recent data for clinical researchers aiming to prevent or eliminate biofilm-associated infections caused by bacterial pathogens. The search was performed considering original research articles published on PubMed, Web of Science and Scopus from 2015 to April 2023, using keywords such as "antibiofilm", "antivirulence", "phytochemicals" and "plant extracts". Over 180 articles were considered for this review with a focus on the priority human pathogens listed by World Health Organization, including Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli. Inhibition and detachment or dismantling of biofilms formed by these pathogens were found using plant-based extract/products or derivative compounds. Although combination of plant-based products and antibiotics were recorded and discussed, this topic is currently poorly explored and only for a reduced number of bacterial species. This review clearly demonstrates that plant-based products or derivative compounds may be a promising therapeutic strategy to eliminate bacterial biofilms and their associated infections. After thoroughly reviewing the vast amount of research carried out over years, it was concluded that plant-based products are mostly able to prevent biofilm formation through inhibition of quorum sensing signals, but also to disrupt mature biofilms developed by multidrug resistant bacteria targeting the biofilm extracellular polymeric substance. Flavonoids and phenolic compounds seemed the most effective against bacterial biofilms.

Bacterial biofilms formed by Staphylococcus aureus and Pseudomonas aeruginosa pose significant challenges in treating cystic fibrosis (CF) airway infections due to their resistance to antibiotics. New therapeutic approaches are urgently needed to treat these chronic infections. This study aimed to investigate the antibiofilm potential of various plant extracts, specifically targeting mucoid and small colony variants of P. aeruginosa and S. aureus and strains. Moreover, it aimed to gain insights into the mechanisms of action and the potential phytochemicals responsible for antibiofilm activity. Solid-liquid extractions were performed on seven biomasses using water and ethanol (70 and 96 %) under controlled conditions, resulting in 21 distinct plant extracts. These extracts were evaluated for extraction yield, antioxidant activity, phenolic content, chemical composition by HPLC-TOF-MS, and antibiofilm activity using a 96-well plate assay, followed by crystal violet staining, bacterial adhesion assessment, and brightfield microscopy. Our findings revealed that aqueous extracts exhibited the highest inhibition of biofilm formation, with cinnamon bark and moringa seeds showing strong antibiofilm activity against both bacterial species. Brightfield microscopy confirmed that these extracts effectively inhibited biofilm formation. Chemical analysis identified key bioactive compounds, including moringin, benzaldehyde, coumarin, and quinic acid, which likely contribute to the observed antibiofilm effects. Recognizing that the antibiofilm properties of moringin, a common compound in both moringa seed and cinnamon bark extracts, remain underexplored, we conducted potential target identification via PharmMapper and molecular docking analyses to provide a foundation for future research. Computational analyses indicated that moringin might inhibit aspartate-semialdehyde dehydrogenase in P. aeruginosa and potentially interact with an unknown target in S. aureus. In conclusion, moringa seed and cinnamon bark extracts demonstrated significant potential for developing new therapies targeting biofilm-associated infections in CF. Further studies are needed to validate the computational predictions, identify the bacterial targets, and elucidate the precise mechanisms behind moringin's antibiofilm activity, which is likely the potential key contributor to the observed activity of the moringa and cinnamon bark extracts.

Pseudomonas aeruginosa is a major cause of chronic respiratory infections in patients with cystic fibrosis (CF), with biofilm formation contributing to its persistence and antibiotic resistance. This study aimed to gain insights into the mechanistic action of succinic acid as a ciprofloxacin adjuvant against clinically relevant CF isolates, including small colony variants and mucoid strains, and a ciprofloxacin-resistant strain grown within CF dense mucus. Time-kill assays in artificial CF mucus, along with planktonic and surface-attached biofilm experiments, were used to assess the activity of succinic acid alone and in combination with sublethal ciprofloxacin concentrations. Succinic acid demonstrated an adjuvant effect of ciprofloxacin against P. aeruginosa grown within CF mucus at pH levels below pKa1 during the early bacterial growth stages. In examining planktonic growth and biofilms under these conditions, we found that succinic acid demonstrated strong antibacterial and antibiofilm properties. Conversely, succinic acid activity decreased at later growth stages, though it enhanced the ciprofloxacin effect, especially against mucoid biofilms. Moreover, we noted that, in dense CF mucus, succinic acid activity was attenuated compared to a non-CF environment, indicating diffusion challenges. These findings underscore the potential of succinic acid as a therapeutic adjuvant for improving antibiotic treatment outcomes and overcoming biofilm-associated resistance in CF.