Mechanizmus účinku a podstata rozdílné citlivosti bakterií k antibakteriálním látkám lipofosfonoxinům

• Main Author: Havlová, Noemi
• Other Authors: Mikušová, Gabriela
• Format: Dissertation
• Language: Czech
• Published: 2018
• Online Access: http://www.nusl.cz/ntk/nusl-450966

Lipophosphonoxins (LPPO) are small synthetic antibacterial compounds targeting the cytoplasmic membrane. 1st generation of LPPO (LPPO I) displays an antimicrobial activity against Gram positive bacteria, however they do not show any activity against Gram negatives. After the modification of the iminosugar module (bearing the positive charge) the 2nd generation of LPPO (LPPO II) were synthetized. LPPO II exhibit broadened activity against Gram positive bacteria and also kill Gram negatives, including multiresistant strains. This work focuses on the mode of action of LPPO - the pore-forming activity of these substances is investigated on model membranes as well as in vivo. It also deals with the nature of different activity against Gram positive and Gram negative bacteria using model bacteria Bacillus subtilis and Escherichia coli. The results show that the insensitivity of Gram negative bacteria against LPPO I is probably caused by the different cell wall structure and the presence of the outer membrane that LPPO are almost unable to overcome. Also, the composition of phospholipids in the target membrane influences the antimicrobial activity of LPPO. Higher proportion of phospholipids with neutral charge reduces the LPPO pore-forming activity but is also responsible for low cytotoxicity in...