Innovative Insights into In Vitro Activity of Colloidal Platinum Nanoparticles against ESBL-Producing Strains of Escherichia coli and Klebsiella pneumoniae.

Growing morbidity and mortality rates due to increase in the number of infections caused by MDR (multi-drug resistant) microorganisms are becoming some of the foremost global health issues. Thus, the need to search for and find novel approaches to fight AMR (antimicrobial resistance) has become obligatory. This study aimed to determine the antimicrobial properties of commercially purchased colloidal platinum nanoparticles by examining the existence and potency of their antibacterial effects and investigating the mechanisms by means of which they express these activities. Antimicrobial properties were investigated with respect to standard laboratory ATCC (American Type Cell Culture) and clinical extended-spectrum beta-lactamase (ESBL)-producing strains of Escherichia (E.) coli and Klebsiella (K.) pneumoniae. Standard microbiological methods of serial microdilution, modulation of microbial cell death kinetics ("time-kill" assays), and biofilm inhibition were used. Bacterial cell wall damage and ROS (reactive oxygen species) levels were assessed in order to explore the mechanisms of platinum nanoparticles' antibacterial activities. Platinum nanoparticles showed strong antibacterial effects against all tested bacterial strains, though their antibacterial effects were found to succumb to time kinetics. Antibiofilm activity was modest overall and significantly effective only against E. coli strains. By measuring extracellular DNA/RNA and protein concentrations, induced bacterial cell wall damage could be assumed. The determination of ROS levels induced by platinum nanoparticles revealed their possible implication in antibacterial activity. We conclude that platinum nanoparticles exhibit potent antibacterial effects against standard laboratory and resistant strains of E. coli and K. pneumoniae. Both, cell wall damage and ROS induction could have important role as mechanisms of antibacterial activity, and, require further investigation.

Design and synthesis of novel antimicrobial peptide scaffolds.

Muramic acid (Mur), a sugar amino acid (SAA), is present in the cell walls of bacteria asN-acetyl muramic acid (MurNAc) where together with ofN-acetylglucosamine (GlcNAc) and peptide makes main building block of peptidoglycan (PGN). It was challenging to incorporate muramic acid as SAA characteristic for bacteria into the peptides and investigate the antimicrobial activity of these scaffolds. Four building units were used in designing the desired peptide: muramic acid, tetrapeptide Leu-Ser-Lys-Leu, Nε-Lys, and Asn. Positions of three components were changeable while the position of Asn was always C-terminal (in linear peptides). The glycopeptide libraries of linear and cyclic peptides were synthesized using solid-phase peptide synthesis (SPPS). The antimicrobial effect of linear and cyclic glycopeptides, as well as the LSKL sequence used as a control, was investigated on several standard laboratory microbial strains. Liner glycopeptide with sequences Leu-Ser-Lys-Leu-Nε-Lys-Mur-Asn was active onStaphylococcus aureus(Gram-positive bacteria). Prepared compounds did not show activity towards applied tumor and normal human cell lines.