A new strain, namely Lysinibacillus sp. BV152.1 was isolated from the rhizosphere of ground ivy (Glechoma hederacea L.) producing metabolites with potent ability to inhibit biofilm formation of an important human pathogens Pseudomonas aeruginosa PAO1, Staphylococcus aureus, and Serratia marcescens. Structural characterization revealed di-rhamnolipids mixture containing rhamnose (Rha)-Rha-C10-C10, Rha-Rha-C8-C10, and Rha-Rha-C10-C12 in the ratio 7:2:1 as the active principle. Purified di-rhamnolipids, as well as commercially available di-rhamnolipids (Rha-Rha-C10-C10, 93%) were used as the substrate for the chemical derivatization for the first time, yielding three semi-synthetic amide derivatives, benzyl-, piperidine-, and morpholine. A comparative study of the anti-biofilm, antibacterial and cytotoxic properties revealed that di-Rha from Lysinibacillus sp. BV152.1 were more potent in biofilm inhibition, both cell adhesion and biofilm maturation, than commercial di-rhamnolipids inhibiting 50% of P. aeruginosa PAO1 biofilm formation at 50 μg mL-1 and 75 μg mL-1, respectively. None of the di-rhamnolipids exhibited antimicrobial properties at concentrations of up to 500 μg mL-1. Amide derivatization improved inhibition of biofilm formation and dispersion activities of di-rhamnolipids from both sources, with morpholine derivative being the most active causing more than 80% biofilm inhibition at concentrations 100 μg mL-1. Semi-synthetic amide derivatives showed increased antibacterial activity against S. aureus, and also showed higher cytotoxicity. Therefore, described di-rhamnolipids are potent anti-biofilm agents and the described approach can be seen as viable approach in reaching new rhamnolipid based derivatives with tailored biological properties.

Infective diseases have become health threat of a global proportion due to appearance and spread of microorganisms resistant to majority of therapeutics currently used for their treatment. Therefore, there is a constant need for development of new antimicrobial agents, as well as novel therapeutic strategies. Quinolines and quinolones, isolated from plants, animals, and microorganisms, have demonstrated numerous biological activities such as antimicrobial, insecticidal, antiinflammatory, antiplatelet, and antitumor. For more than two centuries quinoline/quinolone moiety has been used as a scaffold for drug development and even today it represents an inexhaustible inspiration for design and development of novel semi-synthetic or synthetic agents exhibiting broad spectrum of bioactivities. The structural diversity of synthetized compounds provides high and selective activity attained through different mechanisms of action, as well as low toxicity on human cells. This review describes quinoline and quinolone derivatives with antibacterial, antifungal, anti-virulent, antiviral, and anti-parasitic activities with the focus on the last 10 years literature.

Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 μM). Through detailed structure-activity study, we have identified 7-Cl and 7-CF substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 μM and 63 μM in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w) as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC = 2.5 μM). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.

Copper(ii) complexes with aromatic nitrogen-containing heterocycles are a new class of quorum sensing inhibitors that attenuate virulence without a pronounced effect on the bacterial growth, thus offering a lower risk for resistance development.

Mixed microbial infections caused by Pseudomonas aeruginosa and pathogenic fungi are commonly found in patients with chronic infections and constitute a significant health care burden. The aim of this study was to address the potential polymicrobial antibiofilm activity of pompia and grapefruit essential oils (EOs). The mechanism of antimicrobial activity of EOs was analysed. EOs of pompia and grapefruit inhibited fungal growth with MIC concentrations between 50 and 250 mg L, whereas no effect on P. aeruginosa growth was observed. Both citrus EOs inhibited formation of bacterial and fungal monomicrobial biofilms in concentrations of 50 mg L and were efficient in potentiating the activity of clinically used antimicrobials in vitro The concentration of 10 mg L EOs inhibited mixed biofilm formation composed of P. aeruginosa and Aspergillus fumigatus or Scedosporium apiospermum Citrus EOs affected quorum sensing in P. aeruginosa and caused fast permeabilisation of Candida albicans membrane. Pompia and grapefruit EOs potently inhibited biofilm formation and could be used for the control of common polymicrobial infections.