Mucroporin, the first cationic host defense peptide from the venom of Lychas mucronatus.
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.
Dai
Chao
C
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China.
Ma
Yibao
Y
Zhao
Zhenhuan
Z
Zhao
Ruiming
R
Wang
Qian
Q
Wu
Yingliang
Y
Cao
Zhijian
Z
Li
Wenxin
W
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
D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; D012604:Scorpion Venoms
Annu Rev Immunol. 1995;13:61-92
7612236
Trends Biotechnol. 1998 Feb;16(2):82-8
9487736
N Engl J Med. 2005 Apr 7;352(14):1436-44
15814879
N Engl J Med. 2005 Apr 7;352(14):1445-53
15814880
Cancer Res. 1998 Feb 15;58(4):815-22
9485040
Biochem J. 2001 Oct 1;359(Pt 1):35-45
11563967
Curr Eye Res. 2005 Jul;30(7):505-15
16020284
Eur J Biochem. 2002 Oct;269(19):4799-810
12354111
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D590-2
14681488
Biochem Biophys Res Commun. 2001 Aug 31;286(4):820-5
11520071
Bone Marrow Transplant. 2005 Mar;35(5):497-9
15640812
Trends Immunol. 2002 Jun;23(6):291-6
12072367
Clin Microbiol Rev. 2006 Jul;19(3):491-511
16847082
J Trauma. 2003 Apr;54(4):770-4
12707542
J Leukoc Biol. 1995 Aug;58(2):128-36
7643008
Plast Reconstr Surg. 2002 Apr 1;109(4):1338-43
11964988
J Intern Med. 2004 Apr;255(4):519-20
15049887
N Engl J Med. 2005 Apr 7;352(14):1485-7
15814886
Glia. 2002 Aug;39(2):162-73
12112367
FEBS Lett. 2002 Jun 5;520(1-3):183-4; author reply 185
12044895
Pediatrics. 2003 Jul;112(1 Pt 2):253-8
12837918
Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1327-32
18216255
Trends Microbiol. 2000 Sep;8(9):402-10
10989307
Eur J Biochem. 2000 Aug;267(16):5023-31
10931184
J Biol Chem. 1996 Nov 22;271(47):29537-44
8939880
Mol Cell Proteomics. 2007 May;6(5):882-94
17272268
Adv Exp Med Biol. 2003;531:301-13
12916802
FEBS Lett. 2000 Apr 14;471(2-3):165-8
10767415
Cancer Res. 1998 Nov 1;58(21):4871-9
9809993
J Immunol. 1997 Jun 1;158(11):5120-8
9164927
Drugs. 1998 Dec;56(6):1047-52; discussion 1053-4
9878992
Bioinformatics. 2007 May 1;23(9):1148-55
17341497
Nat Rev Microbiol. 2005 Mar;3(3):238-50
15703760
Cell Mol Life Sci. 2007 Apr;64(7-8):922-33
17310278
Curr Opin Immunol. 2006 Feb;18(1):24-30
16337365
Immunobiology. 2006;211(4):315-22
16697922
Nat Rev Drug Discov. 2003 Oct;2(10):790-802
14526382
Nat Biotechnol. 2003 Dec;21(12):1480-5
14625561
BioDrugs. 2003;17(4):233-40
12899640
Nature. 2005 Oct 13;437(7061):975-80
16222292
Clin Microbiol Infect. 2006 Mar;12 Suppl 1:16-23
16445720
Biochem Biophys Res Commun. 1993 Jul 15;194(1):17-22
8333834
Clin Microbiol Infect. 2006 Apr;12 Suppl 2:3-10
16524422
Peptides. 2004 Feb;25(2):143-50
15062994
JAMA. 2007 Oct 17;298(15):1763-71
17940231
Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):674-81
14967419
Lancet. 1997 Feb 8;349(9049):418-22
9033483
Nature. 2002 Jan 24;415(6870):389-95
11807545
Ann Pharmacother. 2004 Sep;38(9):1449-59
15280512
Indian J Med Microbiol. 2005 Oct;23(4):214-9
16327115
EMBO Rep. 2003 Feb;4(2):114-7
12612596
Int J Antimicrob Agents. 2003 Nov;22(5):465-78
14602364
Drugs. 2003;63(4):389-406
12558461