Hydrophobic interactions in complexes of antimicrobial peptides with bacterial polysaccharides.
Biofilms of Pseudomonas aeruginosa are responsible for chronic lung infections in cystic fibrosis patients, where they are characterized by overproduction of the exopolysaccharide alginate and are recalcitrant to treatment with conventional antibiotics. Cationic antimicrobial peptides (CAPs) are potential alternatives for the treatment of multi-drug-resistant P. aeruginosa. However, alginate in P. aeruginosa biofilms has been proposed to bind these peptides through hydrophobic interactions, consequently reducing their activity [Chan et al., J Biol Chem 2004; 279: 38749-38754]. Here we perform biophysical analyses of the interactions of alginate with a series of novel peptide antibiotics (alpha-CAPs) of prototypic sequence KK-AAAXAAAAAXAAWAAXAAA-KKKK (where X = Phe, Trp or Leu). The hydrophobic interaction interface in alginate was investigated by examining (i) the effects of polysaccharide composition with respect to D-mannuronate and L-guluronate content; (ii) glycan chain length; (iii) alpha-CAP Trp fluorescence; and (iv) 1-anilinonaphthalene-8-sulfonate fluorescence. The results show that, while M and G residues produce equivalent effects, hydrophobic interactions between alginate and alpha-CAPs require a minimal glycan chain length. Peptide interactions with alginate are deduced to be mediated by hydrophobic microdomains comprised of pyranosyl C-H groups that are inducible upon formation of alpha-CAP-alginate complexes due to charge neutralization between the two species.
Kuo
Hsin H
HH
Division of Molecular Structure & Function, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.
Chan
Celine
C
Burrows
Lori L
LL
Deber
Charles M
CM
D000464:Alginates / Q000737:chemistry; D000595:Amino Acid Sequence; D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001419:Bacteria / Q000378:metabolism; D018441:Biofilms; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006603:Hexuronic Acids / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
D000464:Alginates; D000817:Anilino Naphthalenesulfonates; D023181:Antimicrobial Cationic Peptides; D006603:Hexuronic Acids; D010455:Peptides; D011134:Polysaccharides; C007896:guluronic acid; C027132:1-anilino-8-naphthalenesulfonate; C008324:mannuronic acid