Bacterial and fungal biofilm has increased antibiotic resistance and plays an essential role in many persistent diseases. Biofilm-associated chronic infections are difficult to treat and reduce the efficacy of medical devices. This global problem has prompted extensive research to find alternative strategies to fight microbial chronic infections. Plant bioactive metabolites with antibiofilm activity are known to be potential resources to alleviate this problem. The phytochemical screening of some medicinal plants showed different active groups, such as stilbenes, tannins, alkaloids, terpenes, polyphenolics, flavonoids, lignans, quinones, and coumarins. Synergistic effects can be observed in the interaction between plant compounds and conventional drugs. This review analyses and summarises the current knowledge on the synergistic effects of plant metabolites in combination with conventional antimicrobials against biofilms of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The synergism of conventional antimicrobials with plant compounds can modify and inhibit the mechanisms of acquired resistance, reduce undesirable effects, and obtain an appropriate therapeutic effect at lower doses. A deeper knowledge of these combinations and of their possible antibiofilm targets is needed to develop next-generation novel antimicrobials and/or improve current antimicrobials to fight drug-resistant infections attributed to biofilm.

The in vitro cultures of the following three species of the genus Ruta were investigated: R. chalepensis, R. corsica, and R. graveolens. The dynamics of biomass growth and accumulation of secondary metabolites in the 3-, 4-, 5-, 6-, and 7-week growth cycle were analysed. The antioxidant capacity of the methanol extracts obtained from the biomass of the in vitro cultures was also assessed by different in vitro assays: 1,1-diphenyl-2-picrylhydrazil (DPPH), reducing power, and Fe²⁺ chelating activity assays. Moreover, a preliminary screening of the antimicrobial potential of the extracts was performed. The extracts were phytochemically characterized by high-performance liquid chromatography (HPLC), which highlighted the presence of linear furanocoumarins (bergapten, isoimperatorin, isopimpinellin, psoralen, and xanthotoxin) and furoquinoline alkaloids (γ-fagarine, 7-isopentenyloxy-γ-fagarine, and skimmianine). The dominant group of compounds in all the cultures was coumarins (maximum content 1031.5 mg/100 g DW (dry weight), R. chalepensis, 5-week growth cycle). The results of the antioxidant tests showed that the extracts of the three species had varied antioxidant capacity: in particular, the R. chalepensis extract exhibited the best radical scavenging activity (IC₅₀ = 1.665 ± 0.009 mg/mL), while the R. graveolens extract displayed the highest chelating property (IC₅₀ = 0.671 ± 0.013 mg/mL). Finally, all the extracts showed good activity against Staphylococcus aureus with MIC values of 250 μg/mL for the R. corsica extract and 500 μg/mL for both R. graveolens and R. chalepensis extracts.

Levofloxacin (LVF) is an antibacterial drug approved for the treatment of ocular infections. However, due to the low ocular bioavailability, high doses are needed, causing bacterial resistance. Polymeric nanospheres (NPs) loading antibiotic drugs represent the most promising approach to eradicate ocular infections and to treat pathogen resistance. In this study, we have developed chitosan NPs based on sulfobutyl-ether-β-cyclodextrin (CH/SBE-β-CD NPs) for ocular delivery of LVF. CH/SBE-β-CD NPs loading LVF were characterized in terms of encapsulation parameters, morphology, and sizes, in comparison to NPs produced without the macrocycle. Nuclear magnetic resonance and UV–vis spectroscopy studies demonstrated that SBE-β-CD is able to complex LVF and to influence encapsulation parameters of NPs, producing high encapsulation efficiency and LVF loading. The NPs were homogenous in size, with a hydrodynamic radius between 80 and 170 nm and positive zeta potential (ζ) values. This surface property could promote the interaction of NPs with the negatively charged ocular tissue, increasing their residence time and, consequently, LVF efficacy. In vitro, antibacterial activity against Gram-positive and Gram-negative bacteria showed a double higher activity of CH/SBE-β-CD NPs loading LVF compared to the free drug, suggesting that chitosan NPs based on SBE-β-CD could be a useful system for the treatment of ocular infections.

The growing antibiotic resistance phenomenon continues to stimulate the search for new compounds and strategies to combat bacterial infections. In this study, we designed and synthesized a new polycationic macrocyclic compound (2) bearing four N-methyldiethanol ammonium groups clustered and circularly organized by a calix[4]arene scaffold. The in vitro activity of compound 2, alone and in combination with known antibiotics (ofloxacin, chloramphenicol or tetracycline), was assessed against strains of Staphylococcus aureus (ATCC 6538 and methicillin-resistant isolate 15), S. epidermidis (ATCC 35984 and methicillin-resistant isolate 57), and Pseudomonas aeruginosa (ATCC 9027 and antibiotic-resistant isolate 1). Calix[4]arene derivative 2 showed significant antibacterial activity against ATCC and methicillin-resistant Gram positive Staphylococci, improved the stability of tetracycline in water, and in combination with antibiotics enhanced the antibiotic efficacy against Gram negative P. aeruginosa by an additive effect.

Brassica incana Ten. is an edible plant belonging to the Brassicaceae family. In this work, the phenolic composition and the antioxidant and cytotoxic properties of the hydroalcoholic extracts obtained from the leaves and the flowering tops of B. incana grown wild in Sicily (Italy) were studied for the first time. A total of 17 and 20 polyphenolic compounds were identified in the leaf and in the flowering top extracts, respectively, by HPLC-PDA-ESI-MS analysis. Brassica incana extracts showed in vitro antioxidant properties; the leaf extract displayed greater radical scavenging activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test than the flowering top extract (IC₅₀ = 1.306 ± 0.049 mg/mL and 2.077 ± 0.011 mg/mL), which in turn had a stronger ferrous ion chelating ability than the other (IC₅₀ = 0.232 ± 0.002 mg/mL and 1.147 ± 0.016 mg/mL). The cytotoxicity of the extracts against human colorectal adenocarcinoma (CaCo-2) and breast cancer (MCF-7) cell lines was evaluated through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the lactic dehydrogenase (LDH) release determination. The extracts showed cytotoxic efficacy against Caco-2 cells, with the flowering top extract being the most effective (about 90% activity at the highest concentration tested). In the brine shrimp lethality bioassay, the extracts exhibited no toxicity, indicating their potential safety.

A straightforward and green method for the synthesis of gold, silver, and silver chloride nanoparticles (Au NPs and Ag/AgCl NPs) was developed using three different microbial exopolymers (EP) as reducing and stabilizing agents. The exopolysaccharides EPS B3-15 and EPS T14 and the poly-γ-glutamic acid γ-PGA-APA were produced by thermophilic bacteria isolated from shallow hydrothermal vents off the Eolian Islands (Italy) in the Mediterranean Sea. The production of metal NPs was monitored by UV−Vis measurements by the typical plasmon resonance absorption peak and their antimicrobial activity towards Gram-positive and Gram- negative bacteria (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa), as well as fungi (Candida albicans) was investigated. The biological evaluation showed no activity for EP-Au NPs, except against E. coli, whereas EP-Ag NPs exhibited a broad-spectrum of activity. The chemical composition, morphology, and size of EP-Ag NPs were investigated by UV–Vis, zeta potential (ζ), dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM). The best antimicrobial results were obtained for EPS B3-15-Ag NPs and EPS T14-Ag NPs (Minimum Inhibitory Concentration, MIC: 9.37–45 µg/mL; Minimum Bactericidal Concentration/Minimum Fungicidal Concentration, MBC/MFC: 11.25–75 µg/mL).