title: Outer membrane lipoprotein Lpp is Gram-negative bacterial cell surface receptor for cationic antimicrobial peptides.
abstract: Antimicrobial peptides/proteins (AMPs) are important components of the host innate defense mechanisms. Here we demonstrate that the outer membrane lipoprotein, Lpp, of Enterobacteriaceae interacts with and promotes susceptibility to the bactericidal activities of AMPs. The oligomeric Lpp was specifically recognized by several cationic α-helical AMPs, including SMAP-29, CAP-18, and LL-37; AMP-mediated bactericidal activities were blocked by anti-Lpp antibody blocking. Blebbing of the outer membrane and increase in membrane permeability occurred in association with the coordinate internalization of Lpp and AMP. Interestingly, the specific binding of AMP to Lpp was resistant to divalent cations and salts, which were able to inhibit the bactericidal activities of some AMPs. Furthermore, using His-tagged Lpp as a ligand, we retrieved several characterized AMPs, including SMAP-29 and hRNase 7, from a peptide library containing crude mammalian cell lysates. Overall, this study explores a new mechanism and target of antimicrobial activity and provides a novel method for screening of antimicrobials for use against drug-resistant bacteria.
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei 112, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Program in Molecular Medicine, School of Life Sciences, National Yang-Ming, University, 155 Linong St., Sec. 2, Taipei 112, Taiwan.
authors.forename: Ting-Wei
authors.initials: TW
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chiu-Feng
authors.initials: CF
authors.lastname: Wang
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei 112, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Program in Molecular Medicine, School of Life Sciences, National Yang-Ming, University, 155 Linong St., Sec. 2, Taipei 112, Taiwan. Electronic address: ydliao@ibms.sinica.edu.tw.
authors.forename: You-Di
authors.initials: YD
authors.lastname: Liao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data; D055503:Protein Multimerization / Q000187:drug effects; D020836:Protein Structure, Quaternary / Q000187:drug effects; D017433:Protein Structure, Secondary; D021381:Protein Transport / Q000187:drug effects; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D023181:Antimicrobial Cationic Peptides; D001425:Bacterial Outer Membrane Proteins; D011956:Receptors, Cell Surface
references.citation: J Biol Chem. 1986 Jul 5;261(19):8953-7
references.pmid: 3013869
references.citation: Nat Rev Microbiol. 2008 Dec;6(12):893-903
references.pmid: 18997824
references.citation: J Antimicrob Chemother. 2007 Dec;60(6):1206-15
references.pmid: 17878146
references.citation: Mol Biosyst. 2007 May;3(5):317-35
references.pmid: 17460791
references.citation: Cell Mol Life Sci. 2006 Feb;63(4):469-86
references.pmid: 16416029
references.citation: Antimicrob Agents Chemother. 1987 Feb;31(2):230-7
references.pmid: 3032093
references.citation: J Mol Biol. 2000 Jun 16;299(4):1101-12
references.pmid: 10843861
references.citation: J Biol Chem. 2007 Feb 16;282(7):4626-4633
references.pmid: 17150966
references.citation: Nat Immunol. 2005 Jan;6(1):57-64
references.pmid: 15568027
references.citation: Methods Cell Biol. 2010;96:21-45
references.pmid: 20869517
references.citation: J Antimicrob Chemother. 2007 Jun;59(6):1223-9
references.pmid: 17229832
references.citation: Antimicrob Agents Chemother. 1997 Aug;41(8):1738-42
references.pmid: 9257752
references.citation: J Biol Chem. 2010 Mar 19;285(12):8985-94
references.pmid: 20100832
references.citation: Antimicrob Agents Chemother. 1998 Sep;42(9):2206-14
references.pmid: 9736536
references.citation: Eur J Biochem. 2002 Feb;269(4):1181-9
references.pmid: 11856344
references.citation: J Biol Chem. 1994 Aug 5;269(31):19701-6
references.pmid: 8051048
references.citation: Curr Protein Pept Sci. 2005 Feb;6(1):35-51
references.pmid: 15638767
references.citation: Biochem Biophys Res Commun. 2001 Jul 27;285(4):1046-51
references.pmid: 11467858
references.citation: Chembiochem. 2010 Jul 5;11(10):1325-34
references.pmid: 20564281
references.citation: J Biol Chem. 2002 Nov 29;277(48):46779-84
references.pmid: 12244054
references.citation: Infect Immun. 2000 May;68(5):2748-55
references.pmid: 10768969
references.citation: J Bacteriol. 1978 Mar;133(3):1467-71
references.pmid: 346575
references.citation: Antimicrob Agents Chemother. 2001 Jan;45(1):331-4
references.pmid: 11120991
references.citation: Biochim Biophys Acta. 1999 Dec 15;1462(1-2):11-28
references.pmid: 10590300
references.citation: Curr Opin Immunol. 2006 Feb;18(1):24-30
references.pmid: 16337365
references.citation: J Biol Chem. 2001 Feb 23;276(8):5707-13
references.pmid: 11085990
references.citation: J Biol Chem. 1972 Dec 25;247(24):8154-9
references.pmid: 4565677
references.citation: J Invest Dermatol. 2003 May;120(5):810-6
references.pmid: 12713586
references.citation: Biochim Biophys Acta. 1975 Jan 14;375(1):44-53
references.pmid: 1089432
references.citation: J Bacteriol. 1976 Jul;127(1):555-63
references.pmid: 58861
references.citation: Nature. 2002 Jan 24;415(6870):389-95
references.pmid: 11807545
references.citation: Microbes Infect. 2002 Feb;4(2):215-24
references.pmid: 11880055
references.citation: Mol Microbiol. 2011 Mar;79(5):1168-81
references.pmid: 21219470
references.citation: Proc Natl Acad Sci U S A. 1974 Jun;71(6):2396-2400
references.pmid: 4601588