The human cathelicidin antimicrobial peptide LL-37 as a potential treatment for polymicrobial infected wounds

被引:201
作者
Duplantier, Allen J. [1 ]
van Hoek, Monique L. [1 ,2 ]
机构
[1] George Mason Univ, Natl Ctr Biodef & Infect Dis, Manassas, VA 20110 USA
[2] George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA
关键词
antimicrobial peptide; chronic wounds; biofilm; infected wounds; cathelicidin;
D O I
10.3389/fimmu.2013.00143
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Diabetic patients often have ulcers on their lower-limbs that are infected by multiple biofilm-forming genera of bacteria, and the elimination of the biofilm has proven highly successful in resolving such wounds in patients. To that end, antimicrobial peptides have shown potential as a new anti-biofilm approach. The single human cathelicidin peptide LL-37 has been shown to have antimicrobial and anti-biofilm activity against multiple Gram-positive and Gram-negative human pathogens, and have wound-healing effects on the host. The combination of the anti-biofilm effect and wound-healing properties of LL-37 may make it highly effective in resolving polymicrobially infected wounds when topically applied. Such a peptide or its derivatives could be a platform from which to develop new therapeutic strategies to treat biofilm-mediated infections of wounds. This review summarizes known mechanisms that regulate the endogenous levels of LL-37 and discusses the anti-biofilm, antibacterial, and immunological effects of deficient vs. excessive concentrations of LL-37 within the wound environment. Here, we review recent advances in understanding the therapeutic potential of this peptide and other clinically advanced peptides as a potential topical treatment for polymicrobial infected wounds.
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页数:14
相关论文
共 114 条
[1]
Biofilm formation and dispersal in Gram-positive bacteria [J].
Abee, Tjakko ;
Kovacs, Akos T. ;
Kuipers, Oscar P. ;
van der Veen, Stijn .
CURRENT OPINION IN BIOTECHNOLOGY, 2011, 22 (02) :172-179
[2]
Antimicrobial and antibiofilm activity of cathelicidins and short, synthetic peptides against Francisella [J].
Amer, Lilian S. ;
Bishop, Barney M. ;
van Hoek, Monique L. .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 396 (02) :246-251
[3]
Ammons Mary C B, 2010, Recent Pat Antiinfect Drug Discov, V5, P10
[4]
Combined treatment of Pseudomonas aeruginosa biofilm with lactoferrin and xylitol inhibits the ability of bacteria to respond to damage resulting from lactoferrin iron chelation [J].
Ammons, Mary Cloud B. ;
Ward, Loren S. ;
Dowd, Scot ;
James, Garth A. .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2011, 37 (04) :316-323
[5]
In vitro susceptibility of established biofilms composed of a clinical wound isolate of Pseudomonas aeruginosa treated with lactoferrin and xylitol [J].
Ammons, Mary Cloud B. ;
Ward, Loren S. ;
Fisher, Steve T. ;
Wolcott, Randall D. ;
James, Garth A. .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2009, 33 (03) :230-236
[6]
[Anonymous], 2012, DEV PROGRAM LL 37
[7]
Epithelial antimicrobial peptides in host defense against infection [J].
Bals R. .
Respiratory Research, 1 (3)
[8]
Glycosaminoglycans inhibit the antibacterial activity of LL-37 in biological fluids [J].
Baranska-Rybak, W ;
Sonesson, A ;
Nowicki, R ;
Schmidtchen, A .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2006, 57 (02) :260-265
[9]
The human cationic peptide LL-37 induces activation of the extracellular signal-regulated kinase and p38 kinase pathways in primary human monocytes [J].
Bowdish, DME ;
Davidson, DJ ;
Speert, DP ;
Hancock, REW .
JOURNAL OF IMMUNOLOGY, 2004, 172 (06) :3758-3765
[10]
Keratinocyte production of cathelicidin provides direct activity against bacterial skin pathogens [J].
Braff, MH ;
Zaiou, M ;
Fierer, J ;
Nizet, V ;
Gallo, RL .
INFECTION AND IMMUNITY, 2005, 73 (10) :6771-6781