[Antibacterial effect of the antiseptic picloxydine dihydrochloride on conjunctival isolates of gram-negative bacteria]. / Antibakterial'noe deistvie antiseptika pikloksidina digidrokhlorida na kon"yunktival'nye izolyaty gramotritsatel'nykh bakterii.

The preoperative and postoperative use of antiseptics can be an alternative to antibiotics in repeated courses of anti-VEGF therapy for reducing the risk of developing antibiotic resistance in eye microflora. Among gram-negative bacteria, the most frequently isolated pathogen that causes eye infections is Pseudomonas aeruginosa, which is characterized by reduced sensitivity to antibiotics and disinfectants. PURPOSE: To study the effect of the antiseptic picloxydine dihydrochloride on the gram-negative bacteria Escherichia coli, Pseudomonas luteola and P. aeruginosa isolated from the conjunctiva. MATERIAL AND METHODS: The identification of bacterial isolates and study of their sensitivity to antibiotics were carried out using the automated bacteriological analyzer BD Phoenix 100. To determine the bactericidal concentration, the method of serial dilutions of the antiseptic in a liquid nutrient medium was used. The binding of cationic molecules of picloxydine dihydrochloride to bacterial cells was detected by neutralizing the bacterial surface with increasing amounts of antiseptic, and measuring the zeta potential on the Zetasizer Nano ZS analyzer. The ultrastructure of bacterial cells was studied using the two-beam scanning ion-electron microscope Quanta 200 3D. RESULTS: The most resistant was P. aeruginosa. The interaction mechanism of picloxydine dihydrochloride with bacterial cells includes electrostatic binding of positively charged antiseptic molecules to negatively charged cell walls. Picloxydine dihydrochloride has a destructive effect on the bacterial cell wall and plasma membrane, which leads to cell lysis and release of intracellular components. CONCLUSION: Picloxydine dihydrochloride exhibits bactericidal activity against gram-negative conjunctival isolates and is promising for preventive use during repeated courses of intravitreal injections.

Cationic Antiseptics Facilitate Pore Formation in Model Bacterial Membranes.

Antiseptics are an essential line of defense against bacterial and viral infections in modern medical practice. Many of them are supposed to act on microbial membranes. However, the detailed mechanisms of their action are still elusive. Here, we utilized coarse-grained molecular dynamics simulations to investigate interactions of different types of cationic antiseptics (CAs) with a model bacterial membrane. The simulations revealed qualitatively distinct patterns of dynamic and structural alterations of membrane induced by different types of antiseptics although none of them caused disintegration or solubilization of the bilayer even at the highest explored concentration. At the same time, the adsorption of antiseptics rendered membranes more vulnerable to poration under exposure to the external electric field. We further discuss the possible relation of the enhanced pore formation induced by CAs to their cytotoxic action.

Molecular Dynamics Modeling of the Interaction of Cationic Fluorescent Lipid Peroxidation-Sensitive Probes with the Mitochondrial Membrane.

Cardiolipin (CL) plays a central role in lipid peroxidation (LPO) of the mitochondrial inner membrane due to higher content of unsaturated fatty acids in CL in comparison with the other phospholipids. CL oxidation plays an important role in the regulation of various intracellular signaling pathways and its excessive oxidation contributes to the development of various pathologies and, possibly, participates in the aging process. Mitochondria-targeted antioxidants containing triphenylphosphonium (TPP+) effectively protect CL from oxidation. It is assumed that fluorescent probes on the basis of the C11-BODIPY fluorophore sensitive to LPO and containing TPP+ can selectively register CL oxidation. To test this possibility, we carried out a molecular dynamic simulation of such probes in a model mitochondrial membrane. It is shown that the probes are located in the membrane at the same depth as the unsaturated bonds in CL molecules sensitive to oxidation. Increasing the length of the linker that binds the fluorophore and TPP+ residue ha little effect on the position of the probe in the membrane. This indicates the possibility of modifying the linker to increase the selectivity of the probes to CL.