scholarly journals Modulation of Human Complement System by Antimicrobial Peptide Arenicin-1 from Arenicola marina

Marine Drugs ◽  
2018 ◽  
Vol 16 (12) ◽  
pp. 480 ◽  
Author(s):  
Ekaterina Umnyakova ◽  
Nikolay Gorbunov ◽  
Alexander Zhakhov ◽  
Ilia Krenev ◽  
Tatiana Ovchinnikova ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Complement System ◽  
Complement Activation ◽  
Marine Invertebrates ◽  
Cytotoxic Agents ◽  
Arenicola Marina ◽  
Low Concentrations ◽  
Marine Polychaete ◽  
Hypothetical Mechanism

Antimicrobial peptides from marine invertebrates are known not only to act like cytotoxic agents, but they also can display some additional activities in mammalian organisms. In particular, these peptides can modulate the complement system as was described for tachyplesin, a peptide from the horseshoe crab. In this work, we investigated the influence on complement activation of the antimicrobial peptide arenicin-1 from the marine polychaete Arenicola marina. To study effects of arenicin on complement activation in human blood serum, we used hemolytic assays of two types, with antibody sensitized sheep erythrocytes and rabbit erythrocytes. Complement activation was also assessed, by the level of C3a production that was measured by ELISA. We found that the effect of arenicin depends on its concentration. At relatively low concentrations the peptide stimulates complement activation and lysis of target erythrocytes, whereas at higher concentrations arenicin acts as a complement inhibitor. A hypothetical mechanism of peptide action is proposed, suggesting its interaction with two complement proteins, C1q and C3. The results lead to the possibility of the development of new approaches for therapy of diseases connected with complement dysregulation, using peptide regulators derived from natural antimicrobial peptides of invertebrates.

scholarly journals Antimicrobial Peptide Arenicin-1 Derivative Ar-1-(C/A) as Complement System Modulator

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 631
Author(s):  
Ilia A. Krenev ◽  
Ekaterina S. Umnyakova ◽  
Igor E. Eliseev ◽  
Yaroslav A. Dubrovskii ◽  
Nikolay P. Gorbunov ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Cancer Cells ◽  
Disulfide Bond ◽  
Complement System ◽  
Targeted Therapeutics ◽  
Arenicola Marina ◽  
Functional Activities ◽  
Complement Proteins ◽  
Natural Forms ◽  
Therapeutics Development

Antimicrobial peptides (AMPs) are not only cytotoxic towards host pathogens or cancer cells but also are able to act as immunomodulators. It was shown that some human and non-human AMPs can interact with complement proteins and thereby modulate complement activity. Thus, AMPs could be considered as the base for complement-targeted therapeutics development. Arenicins from the sea polychaete Arenicola marina, the classical example of peptides with a β-hairpin structure stabilized by a disulfide bond, were shown earlier to be among the most prospective regulators. Here, we investigate the link between arenicins’ structure and their antimicrobial, hemolytic and complement-modulating activities using the derivative Ar-1-(C/A) without a disulfide bond. Despite the absence of this bond, the peptide retains all important functional activities and also appears less hemolytic in comparison with the natural forms. These findings could help to investigate new complement drugs for regulation using arenicin derivatives.

Antimicrobial peptides from marine invertebrates: Challenges and perspectives in marine antimicrobial peptide discovery

2011 ◽  
Vol 29 (5) ◽  
pp. 519-530 ◽  
Author(s):  
Sigmund V. Sperstad ◽  
Tor Haug ◽  
Hans-Matti Blencke ◽  
Olaf B. Styrvold ◽  
Chun Li ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Marine Invertebrates

Antimicrobial Peptides - Small but Mighty Weapons for Plants to Fight Phytopathogens

2019 ◽  
Vol 26 (10) ◽  
pp. 720-742 ◽  
Author(s):  
Kaushik Das ◽  
Karabi Datta ◽  
Subhasis Karmakar ◽  
Swapan K. Datta
Keyword(s):  
Antimicrobial Peptides ◽  
Durable Resistance ◽  
Defense Responses ◽  
Defense System ◽  
Biotechnological Potential ◽  
Functional Aspects ◽  
Low Concentrations ◽  
Wide Range ◽  
Vital Component ◽  
Pathogen Entry

Antimicrobial Peptides (AMPs) have diverse structures, varied modes of actions, and can inhibit the growth of a wide range of pathogens at low concentrations. Plants are constantly under attack by a wide range of phytopathogens causing massive yield losses worldwide. To combat these pathogens, nature has armed plants with a battery of defense responses including Antimicrobial Peptides (AMPs). These peptides form a vital component of the two-tier plant defense system. They are constitutively expressed as part of the pre-existing first line of defense against pathogen entry. When a pathogen overcomes this barrier, it faces the inducible defense system, which responds to specific molecular or effector patterns by launching an arsenal of defense responses including the production of AMPs. This review emphasizes the structural and functional aspects of different plant-derived AMPs, their homology with AMPs from other organisms, and how their biotechnological potential could generate durable resistance in a wide range of crops against different classes of phytopathogens in an environmentally friendly way without phenotypic cost.

Antimicrobial Peptides: A Promising Avenue for Human Healthcare

2020 ◽  
Vol 21 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Girish M. Bhopale
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Antimicrobial Agents ◽  
Current Status ◽  
Antimicrobial Drugs ◽  
Spectrum Activity ◽  
Low Levels ◽  
Human Healthcare ◽  
Broad Spectrum Activity ◽  
Promising Avenue

Antimicrobial drugs resistant microbes have been observed worldwide and therefore alternative development of antimicrobial peptides has gained interest in human healthcare. Enormous progress has been made in the development of antimicrobial peptide during the last decade due to major advantages of AMPs such as broad-spectrum activity and low levels of induced resistance over the current antimicrobial agents. This review briefly provides various categories of AMP, their physicochemical properties and mechanism of action which governs their penetration into microbial cell. Further, the recent information on current status of antimicrobial peptide development, their applications and perspective in human healthcare are also described.

scholarly journals A mixed chirality α-helix in a stapled bicyclic and a linear antimicrobial peptide revealed by X-ray crystallography

2021 ◽  
Author(s):  
Stéphane Baeriswyl ◽  
Hippolyte Personne ◽  
Ivan Di Bonaventura ◽  
Thilo Köhler ◽  
Christian van Delden ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Crystal Structures ◽  
X Ray ◽  
X Ray Crystallography ◽  
Α Helix

We report the first X-ray crystal structures of mixed chirality α-helices comprising only natural residues as the example of bicyclic and linear membrane disruptive amphiphilic antimicrobial peptides containing seven l- and four d-residues.

scholarly journals Expression of Anti-Lipopolysaccharide Factor Isoform 3 in Chlamydomonas reinhardtii Showing High Antimicrobial Activity

Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 239
Author(s):  
Anguo Li ◽  
Ruihao Huang ◽  
Chaogang Wang ◽  
Qunju Hu ◽  
Hui Li ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Chlamydomonas Reinhardtii ◽  
Penaeus Monodon ◽  
Total Soluble Protein ◽  
Cell Factory ◽  
Gram Positive Bacteria ◽  
Resistance Selection ◽  
Expression Cluster ◽  
Potential Strategy

Antimicrobial peptides are a class of proteins with antibacterial functions. In this study, the anti-lipopolysaccharide factor isoform 3 gene (ALFPm3), encoding an antimicrobial peptide from Penaeus monodon with a super activity was expressed in Chlamydomonas reinhardtii, which would develop a microalga strain that can be used for the antimicrobial peptide production. To construct the expression cluster, namely pH2A-Pm3, the codon optimized ALFPm3 gene was fused with the ble reporter by 2A peptide and inserted into pH124 vector. The glass-bead method was performed to transform pH2A-Pm3 into C. reinhardtii CC-849. In addition to 8 μg/mL zeocin resistance selection, the C. reinhardtii transformants were further confirmed by genomic PCR and RT-PCR. Western blot analysis showed that the C. reinhardtii-derived ALFPm3 (cALFPm3) was successfully expressed in C. reinhardtii transformants and accounted for 0.35% of the total soluble protein (TSP). Furthermore, the results of antibacterial assay revealed that the cALFPm3 could significantly inhibit the growth of a variety of bacteria, including both Gram-negative bacteria and Gram-positive bacteria at a concentration of 0.77 μM. Especially, the inhibition could last longer than 24 h, which performed better than ampicillin. Hence, this study successfully developed a transgenic C. reinhardtii strain, which can produce the active ALFPm3 driven from P. monodon, providing a potential strategy to use C. reinhardtii as the cell factory to produce antimicrobial peptides.

scholarly journals Properties of pyruvate kinase and phosphoenolpyruvate carboxykinase in relation to the direction and regulation of phosphoenolpyruvate metabolism in muscles of the frog and marine invertebrates

1978 ◽  
Vol 174 (3) ◽  
pp. 979-987 ◽  
Author(s):  
Victor A. Zammit ◽  
Eric A. Newsholme
Keyword(s):  
Pyruvate Kinase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Marine Invertebrates ◽  
Adductor Muscle ◽  
Sea Anemone ◽  
Anaerobic Conditions ◽  
Fructose Bisphosphate ◽  
Low Concentrations ◽  
Optimum Ph ◽  
Hill Coefficients

1. The properties of pyruvate kinase and, if present, phosphoenolpyruvate carboxykinase from the muscles of the sea anemone, scallop, oyster, crab, lobster and frog were investigated. 2. In general, the properties of pyruvate kinase from all muscles were similar, except for those of the enzyme from the oyster (adductor muscle); the pH optima were between 7.1 and 7.4, whereas that for oyster was 8.2; fructose bisphosphate lowered the optimum pH of the oyster enzyme from 8.2 to 7.1, but it had no effect on the enzymes from other muscles. Hill coefficients for the effect of the concentration of phosphoenolpyruvate were close to unity in the absence of added alanine for the enzymes from all muscles except oyster adductor muscle; it was 1.5 for this enzyme. Alanine inhibited the enzyme from all muscles except the frog; this inhibition was relieved by fructose bisphosphate. Low concentrations of alanine were very effective with the enzyme from the oyster (50% inhibition was observed at 0.4mm). Fructose bisphosphate activated the enzyme from all muscles, but extremely low concentrations were effective with the oyster enzyme (0.13μm produced 50% activation). 3. In general, the properties of phosphoenolpyruvate carboxykinase from the sea anemone and oyster muscles are similar: the Km values for phosphoenolpyruvate are low (0.10 and 0.13mm); the enzymes require Mn2+ in addition to Mg2+ for activity; and ITP inhibits the enzymes and the inhibition is relieved by alanine. These latter compounds had no effect on enzymes from other muscles. 4. It is suggested that changes in concentrations of fructose bisphosphate, alanine and ITP produce a coordinated mechanism of control of the activities of pyruvate kinase and phosphoenolpyruvate carboxykinase in the sea anemone and oyster muscles, which ensures that phosphoenolpyruvate is converted into oxaloacetate and then into succinate in these muscles under anaerobic conditions. 5. It is suggested that in the muscles of the crab, lobster and frog, phosphoenolpyruvate carboxykinase catalyses the conversion of oxaloacetate into phosphoenolpyruvate. This may be part of a pathway for the oxidation of some amino acids in these muscles.

scholarly journals Beneficial Impacts of Incorporating the Non-Natural Amino Acid Azulenyl-Alanine into the Trp-Rich Antimicrobial Peptide buCATHL4B

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 421
Author(s):  
Areetha R. D’Souza ◽  
Matthew R. Necelis ◽  
Alona Kulesha ◽  
Gregory A. Caputo ◽  
Olga V. Makhlynets
Keyword(s):  
Amino Acid ◽  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Mechanism Of Action ◽  
Bactericidal Activity ◽  
Antimicrobial Agents ◽  
Human Cells ◽  
Side Chains ◽  
Natural Amino Acid ◽  
Proteolytic Stability

Antimicrobial peptides (AMPs) present a promising scaffold for the development of potent antimicrobial agents. Substitution of tryptophan by non-natural amino acid Azulenyl-Alanine (AzAla) would allow studying the mechanism of action of AMPs by using unique properties of this amino acid, such as ability to be excited separately from tryptophan in a multi-Trp AMPs and environmental insensitivity. In this work, we investigate the effect of Trp→AzAla substitution in antimicrobial peptide buCATHL4B (contains three Trp side chains). We found that antimicrobial and bactericidal activity of the original peptide was preserved, while cytocompatibility with human cells and proteolytic stability was improved. We envision that AzAla will find applications as a tool for studies of the mechanism of action of AMPs. In addition, incorporation of this non-natural amino acid into AMP sequences could enhance their application properties.

Prokaryotic selectivity and LPS-neutralizing activity of short antimicrobial peptides designed from the human antimicrobial peptide LL-37

Peptides ◽  
2012 ◽  
Vol 35 (2) ◽  
pp. 239-247 ◽  
Author(s):  
Yong Hai Nan ◽  
Jeong-Kyu Bang ◽  
Binu Jacob ◽  
Il-Seon Park ◽  
Song Yub Shin
Keyword(s):  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Neutralizing Activity

Aberrant activation of complement system in renal grafts is mediated by cold storage

2021 ◽  
Author(s):  
Sorena Lo ◽  
Li Jiang ◽  
Savannah Stacks ◽  
Haixia Lin ◽  
Nirmala Parajuli
Keyword(s):  
Cold Storage ◽  
Complement System ◽  
Complement Activation ◽  
Renal Tubules ◽  
Renal Transplants ◽  
Reducing Conditions ◽  
Tnf Α ◽  
Renal Grafts ◽  
The Impact ◽  
The Complement System

Aberrant complement activation leads to tissue damage during kidney transplantation, and it is recognized as an important target for therapeutic intervention (6, 19, 35, 64). However, it is not clear whether cold storage (CS) triggers the complement pathway in transplanted kidneys. The goal of this study was to determine the impact of CS on complement activation in renal transplants. Male Lewis and Fischer rats were used, and donor rat kidneys were exposed to 4 h or 18 h of CS followed by transplantation (CS+Transplant). To study CS-induced effects, a group with no CS was included in which the kidney was removed and transplanted back to the same rat (autotransplantation, ATx). Complement proteins (C3 and C5b-9) were evaluated with western blotting (reducing and non-reducing conditions) and immunostaining. Western blot of renal extracts or serum indicated that the levels of C3 and C5b-9 increased after CS+Transplant compared to ATx. Quite strikingly, intracellular C3 was profoundly elevated within renal tubules after CS+Transplant but was absent in Sham or ATx groups, which showed only extratubular C3. Similarly, C5b-9 immunofluorescence staining of renal sections showed an increase in C5b-9 deposits in kidneys after CS+Transplant. Real-time PCR (SYBR Green) showed increased expression of CD11b and CD11c, components of complement receptors 3 and 4, respectively, as well as inflammatory markers such as TNF-α. In addition, recombinant TNF-α significantly increased C3 levels in renal cells. Collectively, these results demonstrate that CS activates the complement system in renal transplants.

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