Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies

被引:3322
作者
Hancock, Robert E. W.
Sahl, Hans-Georg
机构
[1] Univ British Columbia, Ctr Microbial Dis & Immun Res, Vancouver, BC V6T 1Z4, Canada
[2] Inst Med Microbiol & Immunol, Dept Pharmaceut Microbiol, D-53115 Bonn, Germany
基金
加拿大健康研究院; 美国国家卫生研究院;
关键词
D O I
10.1038/nbt1267
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Short cationic amphiphilic peptides with antimicrobial and/or immunomodulatory activities are present in virtually every life form, as an important component of ( innate) immune defenses. These host-defense peptides provide a template for two separate classes of antimicrobial drugs. Direct-acting antimicrobial host-defense peptides can be rapid-acting and potent, and possess an unusually broad spectrum of activity; consequently, they have prospects as new antibiotics, although clinical trials to date have shown efficacy only as topical agents. But for these compounds to fulfill their therapeutic promise and overcome clinical setbacks, further work is needed to understand their mechanisms of action and reduce the potential for unwanted toxicity, to make them more resistant to protease degradation and improve serum half-life, as well as to devise means of manufacturing them on a large scale in a consistent and cost-effective manner. In contrast, the role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory ( septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.
引用
收藏
页码:1551 / 1557
页数:7
相关论文
共 39 条
  • [1] Novel antimicrobial compounds identified using synthetic combinatorial library technology
    Blondelle, SE
    Houghten, RA
    [J]. TRENDS IN BIOTECHNOLOGY, 1996, 14 (02) : 60 - 65
  • [2] A re-evaluation of the role of host defence peptides in mammalian immunity
    Bowdish, DME
    Davidson, DJ
    Hancock, REW
    [J]. CURRENT PROTEIN & PEPTIDE SCIENCE, 2005, 6 (01) : 35 - 51
  • [3] Impact of LL-37 on anti-infective immunity
    Bowdish, DME
    Davidson, DJ
    Lau, YE
    Lee, K
    Scott, MG
    Hancock, REW
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 2005, 77 (04) : 451 - 459
  • [4] Using microarray gene signatures to elucidate mechanisms of antibiotic action and resistance
    Brazas, MD
    Hancock, REW
    [J]. DRUG DISCOVERY TODAY, 2005, 10 (18) : 1245 - 1252
  • [5] Lipid II as a target for antibiotics
    Breukink, E
    de Kruijff, B
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (04) : 321 - 332
  • [6] Bacteriocins: Developing innate immunity for food
    Cotter, PD
    Hill, C
    Ross, RP
    [J]. NATURE REVIEWS MICROBIOLOGY, 2005, 3 (10) : 777 - 788
  • [7] Staphylococcus aureus genetic loci impacting growth and survival in multiple infection environments
    Coulter, SN
    Schwan, WR
    Ng, EYW
    Langhorne, MH
    Ritchie, HD
    Westbrock-Wadman, S
    Hufnagle, WO
    Folger, KR
    Bayer, AS
    Stover, CK
    [J]. MOLECULAR MICROBIOLOGY, 1998, 30 (02) : 393 - 404
  • [8] Primate β-defensins -: Structure, function and evolution
    Crovella, S
    Antcheva, N
    Zelezetsky, I
    Boniotto, M
    Pacor, S
    Falzacappa, MVV
    Tossi, A
    [J]. CURRENT PROTEIN & PEPTIDE SCIENCE, 2005, 6 (01) : 7 - 21
  • [9] Comparison of the genomes of human and mouse lays the foundation of genome zoology
    Emes, RD
    Goodstadt, L
    Winter, EE
    Ponting, CP
    [J]. HUMAN MOLECULAR GENETICS, 2003, 12 (07) : 701 - 709
  • [10] Biosynthesis of nonribosomal peptides
    Finking, R
    Marahiel, MA
    [J]. ANNUAL REVIEW OF MICROBIOLOGY, 2004, 58 : 453 - 488