Mechanisms of action of rabbit CAP18 on monolayers and liposomes made from endotoxins or phospholipids.
We have investigated the mechanism of action of the cationic antimicrobial protein (18 kDa) CAP18 on liposomes and monolayers made from phospholipids and enterobacterial lipopolysaccharides (LPS). CAP18 intercalates into lipid matrices composed of LPS from sensitive strains, weaker into those made of LPS from a resistant strain (Proteus mirabilis strain R45) or negatively charged phospholipids, but not into those composed of neutral phosphatidylcholine. From the combination of data obtained with fluorescence resonance energy transfer and Fourier-transform infrared spectroscopy and film balance measurements, it can be concluded that structural differences in the LPS determine the depth of intercalation of CAP18 into the respective lipid matrices. Thus, we identified the L-Arap4N linked to the first Kdo of the LPS of P. mirabilis strain R45 to be responsible for the CAP18 resistance of this strain. These data provide insight into CAP18-mediated effects on the integrity of the outer membrane of Gram-negative bacteria and led to an improved model for rabbit CAP18 membrane interaction.
Research Center Borstel, Center for Medicine and Biosciences, Department of Immunochemistry and Biochemical Microbiology, Parkallee 10, D-23845 Borstel, Germany.
T
T
Gutsmann
M
M
Fix
J W
JW
Larrick
A
A
Wiese
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002240:Carbohydrate Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology*; D054804:Cathelicidins; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry / Q000187:drug effects*; D046911:Macromolecular Substances; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011513:Proteus mirabilis / Q000737:chemistry; D011817:Rabbits; D019779:Salmonella enterica / Q000737:chemistry; D013045:Species Specificity; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054804:Cathelicidins; D008070:Lipopolysaccharides; D008081:Liposomes; D046911:Macromolecular Substances; D010713:Phosphatidylcholines; D010743:Phospholipids