Comparative study of two plasticins: specificity, interfacial behavior, and bactericidal activity.
A comparative study was designed to evaluate the staphylococcidal efficiency of two sequence-related plasticins from the dermaseptin superfamily we screened previously. Their bactericidal activities against Staphylococcus aureus as well as their chemotactic potential were investigated. The impact of the GraS/GraR two-component system involved in regulating resistance to cationic antimicrobial peptides (CAMPs) was evaluated. Membrane disturbing activity was quantified by membrane depolarization assays using the diS-C3 probe and by membrane integrity assays measuring beta-galactosidase activity with recombinant strain ST1065 reflecting compromised membranes and cytoplasmic leakage. Interactions of plasticins with membrane models composed of either zwitterionic lipids mimicking the S. aureus membrane of CAMP-resistant strains or anionic lipids mimicking the negative charge-depleted membrane of CAMP-sensitive strains were analyzed by jointed Brewster angle microscopy (BAM), polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS), and differential scanning calorimetry (DSC) to yield detailed information about the macroscopic interfacial organization, in situ conformation, orientation of the peptides at the lipid-solvent interface, and lipid-phase disturbance. We clearly found evidence of distinct interfacial behaviors of plasticins we linked to the distribution of charges along the peptides and structural interconversion properties at the membrane interface. Our results also suggest that amidation might play a key role in GraS/GraR-mediated CAMP sensing at the bacterial surface.
Joanne
Pierre
P
Universite Pierre et Marie Curie, ER3-Biogenese des signaux peptidiques, 75251 Paris Cedex 05, France.
Falord
Mélanie
M
Chesneau
Olivier
O
Lacombe
Claire
C
Castano
Sabine
S
Desbat
Bernard
B
Auvynet
Constance
C
Nicolas
Pierre
P
Msadek
Tarek
T
El Amri
Chahrazade
C
D000328:Adult; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000633:toxicity*; D023181:Antimicrobial Cationic Peptides / Q000633:toxicity; D002463:Cell Membrane Permeability / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity*; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development*; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000254:growth & development; D041162:Staphylococcus haemolyticus / Q000187:drug effects / Q000254:growth & development
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D005136:Eye Proteins; D006131:Growth Inhibitors; D009419:Nerve Tissue Proteins; C076104:plasticin