Antimicrobial Peptides of the Innate Immune System

Abstract Antimicrobial peptides (AMPs) are ubiquitous components of the insect innate immune system. The model insect Galleria mellonella has at least 18 AMPs, some of which are still uncharacterized in terms of antimicrobial activity. To determine why G. mellonella secretes a repertoire of distinct AMPs following an immune challenge, we selected three different AMPs: cecropin A (CecA), gallerimycin and cobatoxin. We found that cobatoxin was active against Micrococcus luteus at a minimum inhibitory concentration (MIC) of 120 μm, but at 60 μm when co-presented with 4 μm CecA. In contrast, the MIC of gallerimycin presented alone was 60 μm and the co-presentation of CecA did not affect this value. Cobatoxin and gallerimycin were both inactive against Escherichia coli at physiological concentrations, however gallerimycin could potentiate the sublethal dose of CecA (0.25 μm) at a concentration of 30 μm resulting in 100% lethality. The ability of gallerimycin to potentiate the CecA was investigated by flow cytometry, revealing that 30 μm gallerimycin sensitized E. coli cells by inducing membrane depolarization, which intensified the otherwise negligible effects of 0.25 μm CecA. We therefore conclude that G. mellonella maximizes the potential of its innate immune response by the co-presentation of different AMPs that become more effective at lower concentrations when presented simultaneously.

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Molecular characterization of a novel β-defensin isoform from the red-toothed trigger fish, Odonus niger (Ruppel, 1836)

Journal of Genetic Engineering and Biotechnology ◽

10.1186/s43141-021-00175-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

S. Neelima ◽

K. Archana ◽

P. P. Athira ◽

M. V. Anju ◽

V. V. Anooja ◽

...

Keyword(s):

Immune System ◽

Amino Acid ◽

Antimicrobial Peptides ◽

Innate Immune System ◽

Disulfide Bonds ◽

Signal Sequence ◽

Phylogenetic Analyses ◽

Functional Characterization ◽

Innate Immune ◽

Mature Peptide

Abstract Background The concern regarding a post-antibiotic era with increasing drug resistance by pathogens imposes the need to discover alternatives for existing antibiotics. Antimicrobial peptides (AMPs) with their versatile therapeutic properties are a group of promising molecules with curative potentials. These evolutionarily conserved molecules play important roles in the innate immune system of several organisms. The β-defensins are a group of cysteine rich cationic antimicrobial peptides that play an important role in the innate immune system by their antimicrobial activity against the invading pathogens. The present study deals with a novel β-defensin isoform from the red-toothed trigger fish, Odonus niger. Total RNA was isolated from the gills, cDNA was synthesized and the β-defensin isoform obtained by polymerase chain reaction was cloned and subjected to structural and functional characterization in silico. Results A β-defensin isoform could be detected from the gill mRNA of red-toothed trigger fish, Odonus niger. The cDNA encoded a 63 amino acid peptide, β-defensin, with a 20 amino acid signal sequence followed by 43 amino acid cationic mature peptide (On-Def) having a molecular weight of 5.214 kDa and theoretical pI of 8.89. On-Def possessed six highly conserved cysteine residues forming disulfide bonds between C1–C5, C2–C4, and C3–C6, typical of β-defensins. An anionic pro-region was observed prior to the β-defensin domain within the mature peptide. Clustal alignment and phylogenetic analyses revealed On-Def as a group 2 β-defensin. Furthermore, it shared some structural similarities and functional motifs with β-defensins from other organisms. On-Def was predicted to be non-hemolytic with anti-bacterial, anti-viral, anti-fungal, anti-cancer, and immunomodulatory potential. Conclusion On-Def is the first report of a β-defensin from the red-toothed trigger fish, Odonus niger. The antimicrobial profile showed the potential for further studies as a suitable candidate for antimicrobial peptide therapeutics.

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Application of Antimicrobial Peptides of the Innate Immune System in Combination With Conventional Antibiotics—A Novel Way to Combat Antibiotic Resistance?

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2019.00128 ◽

2019 ◽

Vol 9 ◽

Cited By ~ 40

Author(s):

Maria S. Zharkova ◽

Dmitriy S. Orlov ◽

Olga Yu. Golubeva ◽

Oleg B. Chakchir ◽

Igor E. Eliseev ◽

...

Keyword(s):

Antibiotic Resistance ◽

Immune System ◽

Antimicrobial Peptides ◽

Innate Immune System ◽

Innate Immune ◽

Conventional Antibiotics

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Defining principles that influence antimicrobial peptide activity against capsulatedKlebsiella pneumoniae

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2007036117 ◽

2020 ◽

Vol 117 (44) ◽

pp. 27620-27626 ◽

Cited By ~ 2

Author(s):

Renee M. Fleeman ◽

Luis A. Macias ◽

Jennifer S. Brodbelt ◽

Bryan W. Davies

Keyword(s):

Immune System ◽

Antimicrobial Peptides ◽

Innate Immune System ◽

Extracellular Polysaccharide ◽

Innate Immune ◽

Potential Mechanism ◽

Active Peptide ◽

Peptide Analog ◽

Physical Interactions ◽

Strong Antimicrobial Activity

The extracellular polysaccharide capsule ofKlebsiella pneumoniaeresists penetration by antimicrobials and protects the bacteria from the innate immune system. Host antimicrobial peptides are inactivated by the capsule as it impedes their penetration to the bacterial membrane. While the capsule sequesters most peptides, a few antimicrobial peptides have been identified that retain activity against encapsulatedK. pneumoniae,suggesting that this bacterial defense can be overcome. However, it is unclear what factors allow peptides to avoid capsule inhibition. To address this, we created a peptide analog with strong antimicrobial activity toward severalK. pneumoniaestrains from a previously inactive peptide. We characterized the effects of these two peptides onK. pneumoniae, along with their physical interactions withK. pneumoniaecapsule. Both peptides disrupted bacterial cell membranes, but only the active peptide displayed this activity against capsulatedK. pneumoniae. Unexpectedly, the active peptide showed no decrease in capsule binding, but did lose secondary structure in a capsule-dependent fashion compared with the inactive parent peptide. We found that these characteristics are associated with capsule-peptide aggregation, leading to disruption of theK. pneumoniaecapsule. Our findings reveal a potential mechanism for disrupting the protective barrier thatK. pneumoniaeuses to avoid the immune system and last-resort antibiotics.

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Cryptococcus neoformans Cells in Biofilms Are Less Susceptible than Planktonic Cells to Antimicrobial Molecules Produced by the Innate Immune System

Infection and Immunity ◽

10.1128/iai.00995-06 ◽

2006 ◽

Vol 74 (11) ◽

pp. 6118-6123 ◽

Cited By ~ 59

Author(s):

Luis R. Martinez ◽

Arturo Casadevall

Keyword(s):

Immune System ◽

Antimicrobial Peptides ◽

Cryptococcus Neoformans ◽

Innate Immune System ◽

Capsular Polysaccharide ◽

Pathogenic Fungus ◽

Innate Immune ◽

Planktonic Cells ◽

Phagocytic Cells ◽

Immune Effector

ABSTRACT The human pathogenic fungus Cryptococcus neoformans can form biofilms on polystyrene plates and medical devices in a process that requires capsular polysaccharide release. Although biofilms are known to be less susceptible to antimicrobial drugs, little is known about their susceptibility to antimicrobial molecules produced by the innate immune system. In this study, we investigated the susceptibility of C. neoformans cells in biofilm and planktonic states to oxidative and nonoxidative antimicrobial molecules produced by phagocytic cells. The effects of various immune effector molecules on the fungal mass, metabolic activity, and architecture of C. neoformans biofilms were measured by colony counts, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide reduction, and confocal microscopy, respectively. Biofilms were more resistant than planktonic cells to oxidative stress but remained vulnerable to cationic antimicrobial peptides. However, melanized biofilms were significantly less susceptible to antimicrobial peptides than nonmelanized biofilms. These results suggest that the biofilm phenotype increases resistance against host immune mechanisms, a phenomenon that could contribute to the ability of biofilm-forming microbes to establish persistent infections.

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Antimicrobial Peptides from Amphibian Innate Immune System as Potent Antidiabetic Agents: A Literature Review and Bioinformatics Analysis

Journal of Diabetes Research ◽

10.1155/2021/2894722 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Hossein Soltaninejad ◽

Hadi Zare-Zardini ◽

Mahtab Ordooei ◽

Yaser Ghelmani ◽

Akram Ghadiri-Anari ◽

...

Keyword(s):

Immune System ◽

Antimicrobial Peptides ◽

Innate Immune System ◽

Bioinformatics Analysis ◽

Biological Activities ◽

Innate Immune ◽

Antidiabetic Activity ◽

Net Charge ◽

Peptide Family ◽

Negative Side Effects

Antimicrobial peptides, as an important member of the innate immune system, have various biological activities in addition to antimicrobial activity. There are some AMPs with antidiabetic activity, especially those isolated from amphibians. These peptides can induce insulin release via different mechanisms based on peptide type. In this review study, we collected all reported AMPs with antidiabetic activity. We also analyze the sequence and structure of these peptides for evaluation of sequence and structure effect on their antidiabetic activity. Based on this review, the biggest peptide family with antidiabetic activity is temporins with nine antidiabetic peptides. Frogs are the most abundant source of antidiabetic peptides. Bioinformatics analysis showed that an increase of positive net charge and a decrease of hydrophobicity can improve the insulinotropic effect of peptides. Peptides with higher positive net charge and Boman index showed higher activity. Based on this review article, AMPs with antidiabetic activity, especially those isolated from amphibians, can be used as novel antidiabetic drug for type 2 diabetes disease. So, amphibians are potential sources for active peptides which merit further evaluation as novel insulin secretagogues. However, strategy for the increase of stability and positive activity as well as the decrease of negative side effects must be considered.

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Structure and Biological Functions of β-Hairpin Antimicrobial Peptides

Acta Naturae ◽

10.32607/20758251-2015-7-1-37-47 ◽

2015 ◽

Vol 7 (1) ◽

pp. 37-47 ◽

Cited By ~ 23

Author(s):

P. V. Panteleev ◽

I. A. Bolosov ◽

S. V. Balandin ◽

T. V. Ovchinnikova

Keyword(s):

Immune System ◽

Antimicrobial Peptides ◽

Innate Immune System ◽

Structural Organization ◽

Wide Spectrum ◽

Innate Immune ◽

Animal Origin ◽

Biological Functions ◽

First Line ◽

Drug Candidates

Antimicrobial peptides (AMPs) are evolutionarily ancient factors of the innate immune system that serve as a crucial first line of defense for humans, animals, and plants against infection. This review focuses on the structural organization, biosynthesis, and biological functions of AMPs that possess a -hairpin spatial structure. Representatives of this class of AMPs are among the most active antibiotic molecules of animal origin. Due to their wide spectrum of activity and resistance to internal environmental factors, natural -hairpin AMPbased compounds might become the most promising drug candidates.

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Anti-tumor effects of antimicrobial peptides, targets of the innate immune system, against hematopoietic tumors in Drosophila mxc mutants

10.1101/452961 ◽

2018 ◽

Cited By ~ 4

Author(s):

Mayo Araki ◽

Rie Awane ◽

Tetsuya Sato ◽

Yasuyuki Ohkawa ◽

Yoshihiro H. Inoue

Keyword(s):

Immune System ◽

Antimicrobial Peptides ◽

Tumor Cells ◽

Innate Immune System ◽

Fat Body ◽

Human Cancer ◽

Ectopic Expression ◽

Innate Immune ◽

Hematopoietic Tissue ◽

Hematopoietic Organ

AbstractThe innate immune response is the first line of defense against microbial infections. In Drosophila, three immune pathways induce the synthesis of antimicrobial peptides (AMPs) in the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells. However, little is known about their anti-tumor effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval hematopoietic organ called the lymph gland (LG). Here, using RNA-Seq analysis, we found that many immunoresponsive genes, including AMP genes, were up-regulated in the mutants. Down-regulation of these pathways by either a Toll or an imd mutation enhanced the tumor phenotype of the mxc mutants. Conversely, ectopic expression of each of five different AMPs in the fat body significantly suppressed the LG hyperplasia phenotype in the mutants. Thus, we propose that the Drosophila innate immune system can suppress progression of hematopoietic tumors by inducing AMP gene expression. Overexpression of any one of these five AMPs resulted in enhanced apoptosis in the mutant LGs, while no apoptosis signals were detected in controls. We observed that two AMPs, Drosomycin and Defensin, were taken up by circulating hemocyte-like cells, which were associated with LG regions showing reduced cell-to-cell adhesion in the mutants; another AMP, diptericin, was directly localized on the tumors without intermediating hemocytes. These results lead us to conclude that the AMPs have a specific cytotoxic effect that enhance apoptosis exclusively in the tumor cells.Summary statement:Antimicrobial peptides can be associated with tumor cells generated in a hematopoietic tissue in Drosophila mxc mutants and have an anti-tumor effect in suppressing their growth.

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