Relationship between amino acid sequence diversity and antimicrobial activity of Japanese quail cathelicidins

Abstract Background Japanese quail is a low-fat, meat-bird species exhibiting high disease resistance. Cathelicidins (CATHs) are host defense peptides conserved across numerous vertebrate species that play an important role in innate immunity. The activity of host defense peptides can be affected by amino acid substitutions. However, no polymorphisms in avian CATH genes have been reported to date. The aim of this study was to clarify the effect on antimicrobial activity of polymorphisms in CATHs. Results DNA for genomic analyses was extracted from the peripheral blood of 99 randomly selected quail from 6 inbred lines. A total of six, four, four, and six CjCATH3 , CjCATH2 , CjCATHB1 , and CjCATH1 alleles were identified, respectively. Nine haplotypes, including four that were strain specific, were identified in alleles from the CjCATH3 , CjCATH2 , CjCATHB1 , and CjCATH1 loci. In addition, two and one amino acid substitutions (I145F, Q148H, and P245H) predicted by PROVEAN and PolyPhen-2 to have deleterious effects were detected at CjCATH2 and B1, respectively. Synthetic CjCATH2 and B1 peptides exhibited greater antibacterial activity against Escherichia coli than chicken CATH2 and B1, respectively. Furthermore, CjCATHB1*04 peptide exhibited less-potent antimicrobial activity than other CjCATHB1 peptides examined. Conclusions This is the first report of amino acid substitutions accompanied by changes in antibacterial activity in avian CATHs. These findings could be employed as indicators of improvements in the innate immune response in poultry.

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Host Defense Peptides: Immune Modulation and Antimicrobial Activity In Vivo

Antimicrobial Peptides and Innate Immunity ◽

10.1007/978-3-0348-0541-4_13 ◽

2012 ◽

pp. 321-358 ◽

Cited By ~ 3

Author(s):

Nicole J. Afacan ◽

Laure M. Janot ◽

Robert E. W. Hancock

Keyword(s):

Antimicrobial Activity ◽

Host Defense ◽

Immune Modulation ◽

Host Defense Peptides ◽

Defense Peptides

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How Oxygen Availability Affects the Antimicrobial Efficacy of Host Defense Peptides: Lessons Learned from Studying the Copper-Binding Peptides Piscidins 1 and 3

International Journal of Molecular Sciences ◽

10.3390/ijms20215289 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5289 ◽

Cited By ~ 6

Author(s):

Adenrele Oludiran ◽

David S. Courson ◽

Malia D. Stuart ◽

Anwar R. Radwan ◽

John C. Poutsma ◽

...

Keyword(s):

Antimicrobial Activity ◽

Host Defense ◽

Bacterial Species ◽

Membrane Curvature ◽

Lessons Learned ◽

Health Concern ◽

Copper Binding ◽

Bacterial Killing ◽

Host Defense Peptides ◽

Defense Peptides

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the immune system function and directly killing bacteria through membrane disruption and oxidative damage. The copper-binding HDPs piscidin 1 and piscidin 3 have previously shown potent antimicrobial activity against a number of Gram-negative and Gram-positive bacterial species but have never been investigated in an anaerobic environment. Synergy between piscidins and metal ions increases bacterial killing aerobically. Here, we performed growth inhibition and time-kill assays against C. difficile showing that both piscidins suppress proliferation of C. difficile by killing bacterial cells. Microscopy experiments show that the peptides accumulate at sites of membrane curvature. We find that both piscidins are effective against epidemic C. difficile strains that are highly resistant to other stresses. Notably, copper does not enhance piscidin activity against C. difficile. Thus, while antimicrobial activity of piscidin peptides is conserved in aerobic and anaerobic settings, the peptide–copper interaction depends on environmental oxygen to achieve its maximum potency. The development of pharmaceuticals from HDPs such as piscidin will necessitate consideration of oxygen levels in the targeted tissue.

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Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity

Biochimie ◽

10.1016/j.biochi.2010.02.023 ◽

2010 ◽

Vol 92 (9) ◽

pp. 1236-1241 ◽

Cited By ~ 157

Author(s):

Daisuke Takahashi ◽

Sanjeev K. Shukla ◽

Om Prakash ◽

Guolong Zhang

Keyword(s):

Antimicrobial Activity ◽

Host Defense ◽

Target Cell ◽

Structural Determinants ◽

Host Defense Peptides ◽

Cell Selectivity ◽

Defense Peptides

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Corrigendum to “Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity” [Biochimie. Volume 92 (2010) p.1236–1241]

Biochimie ◽

10.1016/j.biochi.2010.12.007 ◽

2011 ◽

Vol 93 (3) ◽

pp. 631

Author(s):

Daisuke Takahashi ◽

Sanjeev K. Shukla ◽

Om Prakash ◽

Guolong Zhang

Keyword(s):

Antimicrobial Activity ◽

Host Defense ◽

Target Cell ◽

Structural Determinants ◽

Host Defense Peptides ◽

Cell Selectivity ◽

Defense Peptides

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Structure-Activity Studies and Therapeutic Potential of Host Defense Peptides of Human Thrombin

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01515-10 ◽

2011 ◽

Vol 55 (6) ◽

pp. 2880-2890 ◽

Cited By ~ 46

Author(s):

Gopinath Kasetty ◽

Praveen Papareddy ◽

Martina Kalle ◽

Victoria Rydengård ◽

Matthias Mörgelin ◽

...

Keyword(s):

Amino Acids ◽

Antimicrobial Activity ◽

Host Defense ◽

Host Defense Peptides ◽

Content Type ◽

Peptide Epitopes ◽

Structure Activity ◽

Human Thrombin ◽

Defense Peptides ◽

Anti Inflammatory

ABSTRACTPeptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteriaEscherichia coliandPseudomonas aeruginosa, the Gram-positive bacteriumStaphylococcus aureus, and the fungusCandida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock andP. aeruginosasepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

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Immunomodulatory Activities of Small Host Defense Peptides

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.5.1727-1732.2005 ◽

2005 ◽

Vol 49 (5) ◽

pp. 1727-1732 ◽

Cited By ~ 218

Author(s):

Dawn M. E. Bowdish ◽

Donald J. Davidson ◽

Monisha G. Scott ◽

Robert E. W. Hancock

Keyword(s):

Amino Acid ◽

Cell Line ◽

Host Defense ◽

Host Cells ◽

Amino Acid Derivative ◽

Human Macrophage ◽

Necrosis Factor Alpha ◽

Host Defense Peptides ◽

Tnf Α ◽

Defense Peptides

ABSTRACT Recent studies have demonstrated that in addition to their antimicrobial activity, cationic host defense peptides, like the human cathelicidin LL-37, perform many activities relating to innate immunity, including the induction or modulation of chemokine and cytokine production, alteration of gene expression in host cells, and inhibition of proinflammatory responses of host cells to bacterial components such as lipopolysaccharide (LPS) in vitro and in vivo. To investigate if these properties are shared by smaller peptides, two cathelicidin peptides derived from bovine neutrophils, the 13-mer indolicidin and Bac2A, a linear 12-amino-acid derivative of bactenecin, were compared to the 37-amino-acid peptide LL-37. Indolicidin, like LL-37, inhibited LPS-induced tumor necrosis factor alpha (TNF-α) secretion, even when added up to an hour after the addition of Escherichia coli O111:B4 LPS to the human macrophage/monocyte-like THP-1 cell line. In contrast, Bac2A demonstrated no significant antiendotoxin activity. At low concentrations, indolicidin and LL-37 acted synergistically to suppress LPS-induced production of TNF-α. Indolicidin was analogous to LL-37 in its ability to induce the production of the chemokine interleukin-8 (IL-8) in a human bronchial cell line, 16HBE14o−, but it was unable to induce production of IL-8 in THP-1 cells. In contrast, Bac2A was unable to induce IL-8 in either cell type. Conversely, Bac2A was chemotactic for THP-1 cells at concentrations between 10 and 100 μg/ml, while indolicidin and LL-37 were not chemotactic at these concentrations for THP-1 cells. This indicates that in addition to the potential for direct microbicidal activity, cationic host defense peptides may have diverse and complementary abilities to modulate the innate immune response.

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Antibacterial Activity of Plant Defensins

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-08-18-0229-cr ◽

2019 ◽

Vol 32 (5) ◽

pp. 507-514 ◽

Cited By ~ 16

Author(s):

Andrew E. Sathoff ◽

Deborah A. Samac

Keyword(s):

Antimicrobial Activity ◽

Innate Immunity ◽

Antibacterial Activity ◽

Host Defense ◽

Significant Role ◽

Higher Plants ◽

Plant Innate Immunity ◽

Host Defense Peptides ◽

Plant Defensins ◽

Wide Range

Plant defensins are antimicrobial host defense peptides expressed in all higher plants. Performing a significant role in plant innate immunity, plant defensins display potent activity against a wide range of pathogens. Vertebrate and invertebrate defensins have well-characterized antibacterial activity, but plant defensins are commonly considered to display antimicrobial activity against only fungi. In this review, we highlight the often-overlooked antibacterial activity of plant defensins. Also, we illustrate methods to evaluate defensins for antibacterial activity and describe the current advances in uncovering their antibacterial modes of action.

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