Outer membrane protein I of Pseudomonas aeruginosa is a target of cationic antimicrobial peptide/protein.
Cationic antimicrobial peptides/proteins (AMPs) are important components of the host innate defense mechanisms against invading microorganisms. Here we demonstrate that OprI (outer membrane protein I) of Pseudomonas aeruginosa is responsible for its susceptibility to human ribonuclease 7 (hRNase 7) and alpha-helical cationic AMPs, instead of surface lipopolysaccharide, which is the initial binding site of cationic AMPs. The antimicrobial activities of hRNase 7 and alpha-helical cationic AMPs against P. aeruginosa were inhibited by the addition of exogenous OprI or anti-OprI antibody. On modification and internalization of OprI by hRNase 7 into cytosol, the bacterial membrane became permeable to metabolites. The lipoprotein was predicted to consist of an extended loop at the N terminus for hRNase 7/lipopolysaccharide binding, a trimeric alpha-helix, and a lysine residue at the C terminus for cell wall anchoring. Our findings highlight a novel mechanism of antimicrobial activity and document a previously unexplored target of alpha-helical cationic AMPs, which may be used for screening drugs to treat antibiotic-resistant bacterial infection.
Lin
Yu-Min
YM
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
Wu
Shih-Jung
SJ
Chang
Ting-Wei
TW
Wang
Chiu-Feng
CF
Suen
Ching-Shu
CS
Hwang
Ming-Jing
MJ
Chang
Margaret Dah-Tsyr
MD
Chen
Yuan-Tsong
YT
Liao
You-Di
YD
D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents / Q000737:chemistry; D003600:Cytosol / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry; D008954:Models, Biological; D011108:Polymers / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D003432:Cross-Linking Reagents; D008070:Lipopolysaccharides; D008074:Lipoproteins; D011108:Polymers