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Multifunctional cationic host defence peptides and their clinical applications

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Abstract

With the rapid rise in the emergence of bacterial strains resistant to multiple classes of antimicrobial agents, there is an urgent need to develop novel antimicrobial therapies to combat these pathogens. Cationic host defence peptides (HDPs) and synthetic derivatives termed innate defence regulators (IDRs) represent a promising alternative approach in the treatment of microbial-related diseases. Cationic HDPs (also termed antimicrobial peptides) have emerged from their origins as nature’s antibiotics and are widely distributed in organisms from insects to plants to mammals and non-mammalian vertebrates. Although their original and primary function was proposed to be direct antimicrobial activity against bacteria, fungi, parasites and/or viruses, cationic HDPs are becoming increasingly recognized as multifunctional mediators, with both antimicrobial activity and diverse immunomodulatory properties. Here we provide an overview of the antimicrobial and immunomodulatory activities of cationic HDPs, and discuss their potential application as beneficial therapeutics in overcoming infectious diseases.

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Abbreviations

AMP:

Antimicrobial peptide

BMAP-27:

Bovine myeloid antimicrobial peptide 27

CPP:

Cell-penetrating peptide

CRAMP:

Cathelin-related antimicrobial peptide

CXCR4:

Chemokine receptor 4

hBD-1:

Human beta-defensin 1

HDP:

Host defence peptide

hLF:

Human lactoferrin

IDR:

Innate defence regulator

IL-10:

Interleukin 10

PMAP-23:

Porcine myeloid antimicrobial peptide 23

LL37:

Human cathelicidin (aka hCAP18)

LPS:

Lipopolysaccharide

LTA:

Lipoteichoic acid

MIC:

Minimum inhibitory concentration

MX-226:

Migenix 226 (aka Omeganan)

TAT:

Trans-activating transcriptional factor (aka Tat)

TNFα:

Tumor necrosis factor alpha

TNFAIP3:

Tumor necrosis factor alpha-induced protein 3 (aka A20)

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Acknowledgments

We gratefully acknowledge financial support from Canadian Institutes for Health Research (CIHR). A.T.Y.Y. received studentships from Canadian Cystic Fibrosis Foundation (CCFF) and the Natural Sciences and Engineering Research Council of Canada (NSERC). R.E.W.H. holds a Canada Research Chair.

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  1. Department of Microbiology and Immunology, Centre for Microbial Diseases and Immunity Research, University of British Columbia, Room 232, 2259 Lower Mall Research Station, Vancouver, BC, V6T 1Z4, Canada

    Amy T. Y. Yeung, Shaan L. Gellatly & Robert E. W. Hancock

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  1. Amy T. Y. Yeung
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  2. Shaan L. Gellatly
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  3. Robert E. W. Hancock
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Correspondence to Robert E. W. Hancock.

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Yeung, A.T.Y., Gellatly, S.L. & Hancock, R.E.W. Multifunctional cationic host defence peptides and their clinical applications. Cell. Mol. Life Sci. 68, 2161–2176 (2011). https://doi.org/10.1007/s00018-011-0710-x

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  • DOI: https://doi.org/10.1007/s00018-011-0710-x

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