scholarly journals Identification of Synthetic and Natural Host Defense Peptides with Leishmanicidal Activity

2016 ◽  
Vol 60 (4) ◽  
pp. 2484-2491 ◽  
Author(s):  
A. K. Marr ◽  
S. Cen ◽  
R. E. W. Hancock ◽  
W. R. McMaster
Keyword(s):  
Host Defense ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Host Defense Peptides ◽  
Content Type ◽  
Leishmanicidal Activity ◽  
Wide Range ◽  
Defense Peptides

ABSTRACTLeishmaniaparasites are a major public health problem worldwide. Effective treatment of leishmaniasis is hampered by the high incidence of adverse effects to traditional drug therapy and the emergence of resistance to current therapeutics. A vaccine is currently not available. Host defense peptides have been investigated as novel therapeutic agents against a wide range of pathogens. Here we demonstrate that the antimicrobial peptide LL-37 and the three synthetic peptides E6, L-1018, and RI-1018 exhibit leishmanicidal activity against promastigotes and intramacrophage amastigotes ofLeishmania donovaniandLeishmania major. We also report that theLeishmaniaprotease/virulence factor GP63 confers protection toLeishmaniafrom the cytolytic properties of alll-form peptides (E6, L-1018, and LL-37) but not thed-form peptide RI-1018. The results suggest that RI-1018, E6, and LL-37 are promising peptides to develop further into components for antileishmanial therapy.

scholarly journals Efficacy of Antimicrobial Peptoids against Mycobacterium tuberculosis

2011 ◽  
Vol 55 (6) ◽  
pp. 3058-3062 ◽  
Author(s):  
Rinki Kapoor ◽  
Patrick R. Eimerman ◽  
Jonathan W. Hardy ◽  
Jeffrey D. Cirillo ◽  
Christopher H. Contag ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cause Of Death ◽  
Host Defense ◽  
Natural Host ◽  
Antituberculosis Drug ◽  
Host Defense Peptides ◽  
Content Type ◽  
Defense Peptides

ABSTRACTTuberculosis is a leading cause of death worldwide. Resistance ofMycobacteriumto antibiotics can make treatments less effective in some cases. We tested selected oligopeptoids—previously reported as mimics of natural host defense peptides—for activity againstMycobacterium tuberculosisand assessed their cytotoxicity. A tetrameric, alkylated, cationic peptoid (1-C134mer) was most potent againstM. tuberculosisand least cytotoxic, whereas an unalkylated analogue, peptoid 14mer, was inactive. Peptoid 1-C134merthus merits further study as a potential antituberculosis drug.

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

2011 ◽  
Vol 55 (6) ◽  
pp. 2880-2890 ◽  
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.

scholarly journals Molecular and Biological Properties of Snakins: The Foremost Cysteine-Rich Plant Host Defense Peptides

2020 ◽  
Vol 6 (4) ◽  
pp. 220
Author(s):  
Tao Su ◽  
Mei Han ◽  
Dan Cao ◽  
Mingyue Xu
Keyword(s):  
Host Defense ◽  
Plant Pathogens ◽  
Biological Activities ◽  
Expression Patterns ◽  
Family Members ◽  
Biological Properties ◽  
Plant Host ◽  
Host Defense Peptides ◽  
Wide Range ◽  
Defense Peptides

Plant host defense peptides (HDPs), also known as antimicrobial peptides (AMPs), are regarded as one of the most prevalent barriers elaborated by plants to combat various infective agents. Among the multiple classes of HDPs, the Snakin class attracts special concern, as they carry 12 cysteine residues, being the foremost cysteine-rich peptides of the plant HDPs. Also, their cysteines are present at very highly conserved positions and arranged in an extremely similar way among different members. Like other plant HDPs, Snakins have been shown to exhibit strong antifungal and antibacterial activity against a wide range of plant pathogens. Moreover, they display diversified biological activities in many aspects of plant growth and the development process. This review is devoted to present the general characters of the Snakin class of plant HDPs, as well as the individual features of different Snakin family members. Specifically, the sequence properties, spatial structures, distributions, expression patterns and biological activities of Snakins are described. In addition, further detailed classification of the Snakin family members, along with their possible mode of action and potential applications in the field of agronomy and pathology are discussed.

scholarly journals LL-37 Opsonizes and Inhibits Biofilm Formation of Aggregatibacter actinomycetemcomitans at Subbactericidal Concentrations

2013 ◽  
Vol 81 (10) ◽  
pp. 3577-3585 ◽  
Author(s):  
Asaf Sol ◽  
Ofir Ginesin ◽  
Stella Chaushu ◽  
Laila Karra ◽  
Shunit Coppenhagen-Glazer ◽  
...  
Keyword(s):  
Host Defense ◽  
Biofilm Formation ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Bactericidal Effect ◽  
Raw 264.7 Cells ◽  
Gingival Tissue ◽  
Host Defense Peptides ◽  
Content Type ◽  
Major Mechanism ◽  
Defense Peptides

ABSTRACTHost defense peptides are immediate responders of the innate immunity that express antimicrobial, immunoregulatory, and wound-healing activities. Neutrophils are a major source for oral host defense peptides, and phagocytosis by neutrophils is a major mechanism for bacterial clearance in the gingival tissue. Dysfunction of or reduction in the numbers of neutrophils or deficiency in the LL-37 host defense peptide was each previously linked with proliferation of oralAggregatibacter actinomycetemcomitanswhich resulted in an aggressive periodontal disease. Surprisingly,A. actinomycetemcomitansshows resistance to high concentrations of LL-37. In this study, we demonstrated that submicrocidal concentrations of LL-37 inhibit biofilm formation byA. actinomycetemcomitansand act as opsonins and agglutinins that greatly enhance its clearance by neutrophils and macrophages. Improved uptake ofA. actinomycetemcomitansby neutrophils was mediated by their opsonization with LL-37. Enhanced phagocytosis and killing ofA. actinomycetemcomitansby murine macrophage-like RAW 264.7 cells were dependent on their preagglutination by LL-37. AlthoughA. actinomycetemcomitansis resistant to the bactericidal effect of LL-37, our results offer a rationale for the epidemiological association between LL-37 deficiency and the expansion of oralA. actinomycetemcomitansand indicate a possible therapeutic use of cationic peptides for host defense.

Antiviral Activities of Human Host Defense Peptides

2020 ◽  
Vol 27 (9) ◽  
pp. 1420-1443 ◽  
Author(s):  
David C. Brice ◽  
Gill Diamond
Keyword(s):  
Host Defense ◽  
Broad Spectrum ◽  
Structural Features ◽  
Host Defense Peptides ◽  
Enveloped Viruses ◽  
Human Host ◽  
Wide Range ◽  
Defense Peptides

Peptides with broad-spectrum antimicrobial activity are found widely expressed throughout nature. As they participate in a number of different aspects of innate immunity in mammals, they have been termed Host Defense Peptides (HDPs). Due to their common structural features, including an amphipathic structure and cationic charge, they have been widely shown to interact with and disrupt microbial membranes. Thus, it is not surprising that human HDPs have activity against enveloped viruses as well as bacteria and fungi. However, these peptides also exhibit activity against a wide range of non-enveloped viruses as well, acting at a number of different steps in viral infection. This review focuses on the activity of human host defense peptides, including alpha- and beta-defensins and the sole human cathelicidin, LL-37, against both enveloped and non-enveloped viruses. The broad spectrum of antiviral activity of these peptides, both in vitro and in vivo suggest that they play an important role in the innate antiviral defense against viral infections. Furthermore, the literature suggests that they may be developed into antiviral therapeutic agents.

scholarly journals The GraS Sensor in Staphylococcus aureus Mediates Resistance to Host Defense Peptides Differing in Mechanisms of Action

2015 ◽  
Vol 84 (2) ◽  
pp. 459-466 ◽  
Author(s):  
Siyang Chaili ◽  
Ambrose L. Cheung ◽  
Arnold S. Bayer ◽  
Yan Q. Xiong ◽  
Alan J. Waring ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Host Defense ◽  
Regulatory System ◽  
Annexin V ◽  
Host Defense Peptides ◽  
Content Type ◽  
Protease Activation ◽  
Defense Peptides ◽  
Sense And Respond ◽  
Assay Conditions

Staphylococcus aureususes the two-component regulatory system GraRS to sense and respond to host defense peptides (HDPs). However, the mechanistic impact of GraS or its extracellular sensing loop (EL) on HDP resistance is essentially unexplored. Strains with null mutations in the GraS holoprotein (ΔgraS) or its EL (ΔEL) were compared for mechanisms of resistance to HDPs of relevant immune sources: neutrophil α-defensin (human neutrophil peptide 1 [hNP-1]), cutaneous β-defensin (human β-defensin 2 [hBD-2]), or the platelet kinocidin congener RP-1. Actions studied by flow cytometry included energetics (ENR); membrane permeabilization (PRM); annexin V binding (ANX), and cell death protease activation (CDP). Assay conditions simulated bloodstream (pH 7.5) or phagolysosomal (pH 5.5) pH contexts.S. aureusstrains were more susceptible to HDPs at pH 7.5 than at pH 5.5, and each HDP exerted a distinct effect signature. The impacts of ΔgraSand ΔΕL on HDP resistance were peptide and pH dependent. Both mutants exhibited defects in ANX response to hNP-1 or hBD-2 at pH 7.5, but only hNP-1 did so at pH 5.5. Both mutants exhibited hyper-PRM, -ANX, and -CDP responses to RP-1 at both pHs and hypo-ENR at pH 5.5. The actions correlated with ΔgraSor ΔΕL hypersusceptibility to hNP-1 or RP-1 (but not hBD-2) at pH 7.5 and to all study HDPs at pH 5.5. An exogenous EL mimic protected mutant strains from hNP-1 and hBD-2 but not RP-1, indicating that GraS and its EL play nonredundant roles inS. aureussurvival responses to specific HDPs. These findings suggest that GraS mediates specific resistance countermeasures to HDPs in immune contexts that are highly relevant toS. aureuspathogenesis in humans.

scholarly journals Host Defense Peptide Resistance Contributes to Colonization and Maximal Intestinal Pathology by Crohn's Disease-Associated Adherent-Invasive Escherichia coli

2014 ◽  
Vol 82 (8) ◽  
pp. 3383-3393 ◽  
Author(s):  
Joseph B. McPhee ◽  
Cherrie L. Small ◽  
Sarah A. Reid-Yu ◽  
John R. Brannon ◽  
Hervé Le Moual ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Host Defense ◽  
Bacterial Killing ◽  
Host Defense Peptides ◽  
Content Type ◽  
Host Defense Peptide ◽  
Defense Peptides ◽  
High Level

ABSTRACTHost defense peptides secreted by colonocytes and Paneth cells play a key role in innate host defenses in the gut. In Crohn's disease, the burden of tissue-associatedEscherichia colicommonly increases at epithelial surfaces where host defense peptides concentrate, suggesting that this bacterial population might actively resist this mechanism of bacterial killing. Adherent-invasiveE. coli(AIEC) is associated with Crohn's disease; however, the colonization determinants of AIEC in the inflamed gut are undefined. Here, we establish that host defense peptide resistance contributes to host colonization by Crohn's-associated AIEC. We identified a plasmid-encoded genomic island (called PI-6) in AIEC strain NRG857c that confers high-level resistance to α-helical cationic peptides and α- and β-defensins. Deletion of PI-6 sensitized strain NRG857c to these host defense molecules, reduced its competitive fitness in a mouse model of infection, and attenuated its ability to induce cecal pathology. This phenotype is due to two genes in PI-6,arlA, which encodes a Mig-14 family protein implicated in defensin resistance, andarlC, an OmpT family outer membrane protease. Implicit in these findings are new bacterial targets whose inhibition might limit AIEC burden and disease in the gut.

Geographically Distinct Expression Profile of Host Defense Peptides in the Skin of the Chinese Odorous Frog, Odorrana margaretae

2014 ◽  
Vol 4 (4) ◽  
pp. 288-297
Author(s):  
LING Guiying ◽  
LI Li ◽  
GAO Jiuxiang ◽  
YU Haining ◽  
WANG Yipeng ◽  
...  
Keyword(s):  
Host Defense ◽  
Expression Profile ◽  
Host Defense Peptides ◽  
Defense Peptides

Human Host Defense Peptides - Role in Maintaining Human Homeostasis and Pathological Processes

2017 ◽  
Vol 24 (7) ◽  
pp. 654-672 ◽  
Author(s):  
Malgorzata Anna Dawgul ◽  
Katarzyna E. Greber ◽  
Wieslaw Sawicki ◽  
Wojciech Kamysz
Keyword(s):  
Host Defense ◽  
Host Defense Peptides ◽  
Human Host ◽  
Defense Peptides

scholarly journals Cyclotide host-defense tailored for species and environments in violets from the Canary Islands

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Blazej Slazak ◽  
Klara Kaltenböck ◽  
Karin Steffen ◽  
Martyna Rogala ◽  
Priscila Rodríguez-Rodríguez ◽  
...  
Keyword(s):  
Host Defense ◽  
Canary Islands ◽  
Cyclic Peptides ◽  
Fusarium Culmorum ◽  
Host Defense Peptides ◽  
Biological Assays ◽  
Minimal Inhibitory Concentrations ◽  
Wide Range ◽  
The Common ◽  
Teide Volcano

AbstractCyclotides are cyclic peptides produced by plants. Due to their insecticidal properties, they are thought to be involved in host defense. Violets produce complex mixtures of cyclotides, that are characteristic for each species and variable in different environments. Herein, we utilized mass spectrometry (LC–MS, MALDI-MS), transcriptomics and biological assays to investigate the diversity, differences in cyclotide expression based on species and different environment, and antimicrobial activity of cyclotides found in violets from the Canary Islands. A wide range of different habitats can be found on these islands, from subtropical forests to dry volcano peaks at high altitudes. The islands are inhabited by the endemic Viola palmensis, V. cheiranthifolia, V. anagae and the common V. odorata. The number of cyclotides produced by a given species varied in plants from different environments. The highest diversity was noted in V. anagae which resides in subtropical forest and the lowest in V. cheiranthifolia from the Teide volcano. Transcriptome sequencing and LC–MS were used to identify 23 cyclotide sequences from V. anagae. Cyclotide extracts exhibited antifungal activities with the lowest minimal inhibitory concentrations noted for V. anagae (15.62 μg/ml against Fusarium culmorum). The analysis of the relative abundance of 30 selected cyclotides revealed patterns characteristic to both species and populations, which can be the result of genetic variability or environmental conditions in different habitats. The current study exemplifies how plants tailor their host defense peptides for various habitats, and the usefulness of cyclotides as markers for chemosystematics.

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