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.

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Pseudomonas aeruginosa has been amongst the top 10 'superbugs' worldwide and is causing infections with poor outcomes in both humans and animals. From 202 P. aeruginosa isolates (n = 121 animal and n = 81 human), 40 were selected on the basis of biofilm-forming ability and were comparatively characterized in terms of virulence determinants to the type strain P. aeruginosa PAO1. Biofilm formation, pyocyanin and hemolysin production, and bacterial motility patterns were compared with the ability to kill human cell line A549 in vitro. On average, there was no significant difference between levels of animal and human cytotoxicity, while human isolates produced higher amounts of pyocyanin, hemolysins and showed increased swimming ability. Non-parametric statistical analysis identified the highest positive correlation between hemolysis and the swarming ability. For the first time an ensemble machine learning approach used on the in vitro virulence data determined the highest relative predictive importance of the submerged biofilm formation for the cytotoxicity, as an indicator of the infection ability. The findings from the in vitro study were validated in vivo using zebrafish (Danio rerio) embryos. This study highlighted no major differences between P. aeruginosa species isolated from animal and human infections and the importance of pyocyanin production in cytotoxicity and infection ability.

Combination therapy may be applied in the case of gold(iii) and silver(i) complexes with aromatic nitrogen-containing heterocycles to improve their antimicrobial activity and reduce toxic-side effects.

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Silver(i) complexes with pyridine-4,5-dicarboxylates show significant activity against clinical isolates from the milk of a cow diagnosed with mastitis.

Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becaming increasing difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option.Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype's anti-virulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC 50 =12 μM), biofilm formation (BFIC 50 =50 μM), and motility. Experimentally, compound's activity is achieved through competitive inhibition of PqsR, and structure-activity data was rationalized using molecular docking studies.

Three new silver(I) complexes [Ag(NO3)(tia)(H2O)]n (Ag1), [Ag(CF3SO3)(1,8-naph)]n (Ag2) and [Ag2(1,8-naph)2(H2O)1.2](PF6)2 (Ag3), where tia is thianthrene and 1,8-naph is 1,8-naphthyridine, were synthesized and structurally characterized by different spectroscopic and electrochemical methods and their crystal structures were determined by single-crystal X-ray diffraction analysis. Their antimicrobial potential was evaluated against four bacterial and three Candida species, and the obtained results revealed that these complexes showed significant activity toward the Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and the investigated Candida species with minimal inhibitory concentration (MIC) values in the range 1.56–7.81 μg/mL. On the other hand, tia and 1,8-naph ligands were not active against the investigated strains, suggesting that their complexation with Ag(I) ion results in the formation of antimicrobial compounds. Moreover, low toxicity of the complexes was detected by in vivo model Caenorhabditis elegans. The interaction of the complexes with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied to evaluate their binding affinity towards these biomolecules for possible insights into the mode of antimicrobial activity. The binding affinity of Ag1–3 to BSA was higher than that for DNA, indicating that proteins could be more favorable binding sites for these complexes in comparison to the nucleic acids.