title: Mucroporin, the first cationic host defense peptide from the venom of Lychas mucronatus.
abstract: The misuse of antibiotics has led our age to a dangerous edge, as antibiotic-resistant pathogens appear to evolve more quickly than antibiotics are invented. Thus, new agents to treat bacterial infection are badly needed. Cationic host defense peptides are on the first line of a host defense system and are thought to be good candidates for treating bacterial infection. Here, a novel cationic host defense peptide, mucroporin, was cloned and characterized from the venom of Lychas mucronatus. The MIC for Staphylococcus aureus was 25 microg/ml, including antibiotic-resistant pathogens. Based on the molecular template of mucroporin, mucroporin-M1 was designed by amino acid substitution. The MIC for S. aureus was 5 microg/ml, including the antibiotic-resistant pathogens methicillin-resistant S. aureus, methicillin-resistant coagulase-negative Staphylococcus, penicillin-resistant S. aureus, and penicillin-resistant S. epidermidis. Moreover, mucroporin-M1 also inhibited gram-negative bacteria. The modes of action of mucroporin and mucroporin-M1 were both rapid killing by disrupting the cell membrane of bacteria, and the number of surviving bacteria was reduced by about 4 to 5 orders of magnitude immediately after peptide delivery. These results showed that mucroporin could be considered a potential anti-infective drug, especially for treating antibiotic-resistant pathogens.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Dai
authors.forename: Yibao
authors.initials: Y
authors.lastname: Ma
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Zhao
authors.forename: Ruiming
authors.initials: R
authors.lastname: Zhao
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cao
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000494:pharmacology; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D012604:Scorpion Venoms / Q000235:genetics* / Q000494:pharmacology; D012605:Scorpions / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; D012604:Scorpion Venoms
references.citation: Annu Rev Immunol. 1995;13:61-92
references.pmid: 7612236
references.citation: Trends Biotechnol. 1998 Feb;16(2):82-8
references.pmid: 9487736
references.citation: N Engl J Med. 2005 Apr 7;352(14):1436-44
references.pmid: 15814879
references.citation: N Engl J Med. 2005 Apr 7;352(14):1445-53
references.pmid: 15814880
references.citation: Cancer Res. 1998 Feb 15;58(4):815-22
references.pmid: 9485040
references.citation: Biochem J. 2001 Oct 1;359(Pt 1):35-45
references.pmid: 11563967
references.citation: Curr Eye Res. 2005 Jul;30(7):505-15
references.pmid: 16020284
references.citation: Eur J Biochem. 2002 Oct;269(19):4799-810
references.pmid: 12354111
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D590-2
references.pmid: 14681488
references.citation: Biochem Biophys Res Commun. 2001 Aug 31;286(4):820-5
references.pmid: 11520071
references.citation: Bone Marrow Transplant. 2005 Mar;35(5):497-9
references.pmid: 15640812
references.citation: Trends Immunol. 2002 Jun;23(6):291-6
references.pmid: 12072367
references.citation: Clin Microbiol Rev. 2006 Jul;19(3):491-511
references.pmid: 16847082
references.citation: J Trauma. 2003 Apr;54(4):770-4
references.pmid: 12707542
references.citation: J Leukoc Biol. 1995 Aug;58(2):128-36
references.pmid: 7643008
references.citation: Plast Reconstr Surg. 2002 Apr 1;109(4):1338-43
references.pmid: 11964988
references.citation: J Intern Med. 2004 Apr;255(4):519-20
references.pmid: 15049887
references.citation: N Engl J Med. 2005 Apr 7;352(14):1485-7
references.pmid: 15814886
references.citation: Glia. 2002 Aug;39(2):162-73
references.pmid: 12112367
references.citation: FEBS Lett. 2002 Jun 5;520(1-3):183-4; author reply 185
references.pmid: 12044895
references.citation: Pediatrics. 2003 Jul;112(1 Pt 2):253-8
references.pmid: 12837918
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1327-32
references.pmid: 18216255
references.citation: Trends Microbiol. 2000 Sep;8(9):402-10
references.pmid: 10989307
references.citation: Eur J Biochem. 2000 Aug;267(16):5023-31
references.pmid: 10931184
references.citation: J Biol Chem. 1996 Nov 22;271(47):29537-44
references.pmid: 8939880
references.citation: Mol Cell Proteomics. 2007 May;6(5):882-94
references.pmid: 17272268
references.citation: Adv Exp Med Biol. 2003;531:301-13
references.pmid: 12916802
references.citation: FEBS Lett. 2000 Apr 14;471(2-3):165-8
references.pmid: 10767415
references.citation: Cancer Res. 1998 Nov 1;58(21):4871-9
references.pmid: 9809993
references.citation: J Immunol. 1997 Jun 1;158(11):5120-8
references.pmid: 9164927
references.citation: Drugs. 1998 Dec;56(6):1047-52; discussion 1053-4
references.pmid: 9878992
references.citation: Bioinformatics. 2007 May 1;23(9):1148-55
references.pmid: 17341497
references.citation: Nat Rev Microbiol. 2005 Mar;3(3):238-50
references.pmid: 15703760
references.citation: Cell Mol Life Sci. 2007 Apr;64(7-8):922-33
references.pmid: 17310278
references.citation: Curr Opin Immunol. 2006 Feb;18(1):24-30
references.pmid: 16337365
references.citation: Immunobiology. 2006;211(4):315-22
references.pmid: 16697922
references.citation: Nat Rev Drug Discov. 2003 Oct;2(10):790-802
references.pmid: 14526382
references.citation: Nat Biotechnol. 2003 Dec;21(12):1480-5
references.pmid: 14625561
references.citation: BioDrugs. 2003;17(4):233-40
references.pmid: 12899640
references.citation: Nature. 2005 Oct 13;437(7061):975-80
references.pmid: 16222292
references.citation: Clin Microbiol Infect. 2006 Mar;12 Suppl 1:16-23
references.pmid: 16445720
references.citation: Biochem Biophys Res Commun. 1993 Jul 15;194(1):17-22
references.pmid: 8333834
references.citation: Clin Microbiol Infect. 2006 Apr;12 Suppl 2:3-10
references.pmid: 16524422
references.citation: Peptides. 2004 Feb;25(2):143-50
references.pmid: 15062994
references.citation: JAMA. 2007 Oct 17;298(15):1763-71
references.pmid: 17940231
references.citation: Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):674-81
references.pmid: 14967419
references.citation: Lancet. 1997 Feb 8;349(9049):418-22
references.pmid: 9033483
references.citation: Nature. 2002 Jan 24;415(6870):389-95
references.pmid: 11807545
references.citation: Ann Pharmacother. 2004 Sep;38(9):1449-59
references.pmid: 15280512
references.citation: Indian J Med Microbiol. 2005 Oct;23(4):214-9
references.pmid: 16327115
references.citation: EMBO Rep. 2003 Feb;4(2):114-7
references.pmid: 12612596
references.citation: Int J Antimicrob Agents. 2003 Nov;22(5):465-78
references.pmid: 14602364
references.citation: Drugs. 2003;63(4):389-406
references.pmid: 12558461