Lipophosphonoxins (LPPOs) are small modular synthetic antibacterial compounds that target the cytoplasmic membrane. First-generation LPPOs (LPPO I) exhibit an antimicrobial activity against Gram-positive bacteria; however they do not exhibit any activity against Gram-negatives. Second-generation LPPOs (LPPO II) also exhibit broadened activity against Gram-negatives. We investigated the reasons behind this different susceptibility of bacteria to the two generations of LPPOs using model membranes and the living model bacteria Bacillus subtilis and Escherichia coli. We show that both generations of LPPOs form oligomeric conductive pores and permeabilize the bacterial membrane of sensitive cells. LPPO activity is not affected by the value of the target membrane potential, and thus they are also active against persister cells. The insensitivity of Gram-negative bacteria to LPPO I is probably caused by the barrier function of the outer membrane with LPS. LPPO I is almost incapable of overcoming the outer membrane in living cells, and the presence of LPS in liposomes substantially reduces their activity. Further, the antimicrobial activity of LPPO is also influenced by the phospholipid composition of the target membrane. A higher proportion of phospholipids with neutral charge such as phosphatidylethanolamine or phosphatidylcholine reduces the LPPO permeabilizing potential.

• MeSH
• antibakteriální látky chemická syntéza   farmakologie   MeSH
• Bacillus subtilis chemie   cytologie   účinky léků   MeSH
• Escherichia coli chemie   cytologie   účinky léků   MeSH
• fosfatidylcholiny analýza   metabolismus   MeSH
• fosfatidylethanolaminy analýza   metabolismus   MeSH
• kationické antimikrobiální peptidy chemická syntéza   farmakologie   MeSH
• lipidové dvojvrstvy MeSH
• membránové potenciály účinky léků   MeSH
• mikrobiální testy citlivosti MeSH
• permeabilita buněčné membrány MeSH
• vnější bakteriální membrána chemie   účinky léků   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• fosfatidylcholiny MeSH
• fosfatidylethanolaminy MeSH
• kationické antimikrobiální peptidy MeSH
• lipidové dvojvrstvy MeSH
• phosphatidylethanolamine MeSH Prohlížeč