scholarly journals The rumen eukaryotome is a source of novel antimicrobial peptides with therapeutic potential

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lucy A. Onime ◽  
Linda B. Oyama ◽  
Benjamin J. Thomas ◽  
Jurnorain Gani ◽  
Peter Alexander ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Infections ◽  
Therapeutic Potential ◽  
Membrane Damage ◽  
Therapeutic Index ◽  
Antimicrobial Activities ◽  
Transmission Electron ◽  
Helical Peptide ◽  
Further Development

Abstract Background The rise of microbial antibiotic resistance is a leading threat to the health of the human population. As such, finding new approaches to tackle these microbes, including development of novel antibiotics is vital. Results In this study, we mined a rumen eukaryotic metatranscriptomic library for novel Antimicrobial peptides (AMPs) using computational approaches and thereafter characterised the therapeutic potential of the AMPs. We identified a total of 208 potentially novel AMPs from the ruminal eukaryotome, and characterised one of those, namely Lubelisin. Lubelisin (GIVAWFWRLAR) is an α-helical peptide, 11 amino acid long with theoretical molecular weight of 1373.76 D. In the presence of Lubelisin, strains of methicillin-resistant Staphylococcus aureus (MRSA) USA300 and EMRSA-15 were killed within 30 min of exposure with ≥103 and 104 CFU/mL reduction in viable cells respectively. Cytotoxicity of Lubelisin against both human and sheep erythrocytes was low resulting in a therapeutic index of 0.43. Membrane permeabilisation assays using propidium iodide alongside transmission electron microscopy revealed that cytoplasmic membrane damage may contribute to the antimicrobial activities of Lubelisin. Conclusions We demonstrate that the rumen eukaryotome is a viable source for the discovery of antimicrobial molecules for the treatment of bacterial infections and further development of these may provide part of the potential solution to the ongoing problem of antimicrobial resistance. The role of these AMPs in the ecological warfare within the rumen is also currently unknown.

Silver Oxide–Copper Oxide Nanocomposite Preparation and Antimicrobial Activity as a Source for the Treatment of Fish Diseases

2017 ◽  
pp. 140-151
Author(s):  
Sayed Reza Shaffiey ◽  
Sayedeh Fatemeh Shaffiey
Keyword(s):  
Aeromonas Hydrophila ◽  
Bacterial Infections ◽  
Antimicrobial Activities ◽  
Cuo Nanoparticles ◽  
Negative Bacterium ◽  
Electron Micrograph ◽  
X Ray Diffraction ◽  
Gram Negative ◽  
Transmission Electron ◽  
Scanning Electron

Aeromonas hydrophila is a heterotrophic, gram negative bacterium which is primary or secondary cause of ulcers, fin rot, tail rot, and hemorrhagic septicaemia in fish. The treatments for this infection are only restricted to some antibiotics. So, novel materials are being searched for combating with bacterial infections and the resulting consequences. In this chapter, Ag2O/CuO nanocomposites were synthesized chemically and characterized by X-ray diffraction (XRD), scanning electron micrograph (SEM) and transmission electron microscope (TEM). The antimicrobial activities of Ag2O/CuO nanoparticles (NPs), was checked by both well diffusion and turbidometric (spectrophotometric) method. Synthesized nanoparticles exhibited their antimicrobial efficacy in both the standard inhibitory assays; these results thus provide a scope for further research on the application of Ag2O/CuO nanoparticles as disinfectant and/or antibiotic in the fishery industry.

The Role of Formyl Peptide Receptors for Immunomodulatory Activities of Antimicrobial Peptides and Peptidomimetics

2018 ◽  
Vol 24 (10) ◽  
pp. 1100-1120 ◽  
Author(s):  
Sarah Line Skovbakke ◽  
Andre Holdfeldt ◽  
Huamei Forsman ◽  
Johan Bylund ◽  
Henrik Franzyk
Keyword(s):  
Antimicrobial Peptides ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Chemical Properties ◽  
Immunomodulatory Activity ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
Natural And Synthetic

In recent years, the therapeutic potential of antimicrobial peptides (AMPs) as immunomodulators has become generally accepted. Nevertheless, only very few AMP-based compounds have progressed into clinical trials. This paradox may be explained by the fact, that some of the intrinsic properties of natural peptides, such as proteolytic and oxidative instability, render them inconvenient as therapeutics. Therefore, substantial research efforts have been dedicated to mimic the physico-chemical properties as well as biological activities of AMPs by designing and identifying more stable peptidomimetics displaying analogous immunomodulatory activity profiles. Neutrophils play key roles in host defense as major effector cells in clearance of pathogens by phagocytosis and by regulating other processes of innate immunity as well as by promoting resolution of inflammation. Several aspects of these effects are correlated to their expression of formyl peptide receptors (FPRs) that have been shown to be targets of both natural and synthetic antimicrobial peptides. In the present review recent findings highlighting the role of FPRs in mediating immunomodulatory activities of natural and synthetic AMPs as well as of stabilized peptidomimetics are discussed, and prospects for future development of immunomodulatory therapeutics are presented.

scholarly journals The Role of Endogenous Antimicrobial Peptides in Modulating Innate Immunity of the Ocular Surface in Dry Eye Diseases

2021 ◽  
Vol 22 (2) ◽  
pp. 721
Author(s):  
Youssof Eshac ◽  
Rachel L. Redfern ◽  
Vinay Kumar Aakalu
Keyword(s):  
Antimicrobial Peptides ◽  
Dry Eye ◽  
Ocular Surface ◽  
Immune Modulation ◽  
Therapeutic Potential ◽  
Eye Diseases ◽  
Innate Immune ◽  
Disease States ◽  
Ocular Surface Diseases

The ocular surface has the challenging responsibility of maintaining a clear moist refractive surface while protecting the eye from exogenous pathogens and the environment. Homeostasis of the ocular surface, including its innate immune components, is altered in ocular surface disease states. In this review, we focus on antimicrobial peptides and the role they play in the immune response of the ocular surface during healthy states and dry eye diseases. Antimicrobial peptides are of special interest to the study of the ocular surface because of their various roles that include microbial threat neutralization, wound healing, and immune modulation. This review explores current literature on antimicrobial peptides in ocular surface diseases and discusses their therapeutic potential in ocular surface diseases and dry eye.

scholarly journals Bactericidal Activity of Mammalian Cathelicidin-Derived Peptides

2000 ◽  
Vol 68 (5) ◽  
pp. 2748-2755 ◽  
Author(s):  
Sue M. Travis ◽  
Norma N. Anderson ◽  
William R. Forsyth ◽  
Cesar Espiritu ◽  
Barbara D. Conway ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptides ◽  
Bactericidal Activity ◽  
Bacterial Infections ◽  
Therapeutic Potential ◽  
Solid Phase ◽  
Antimicrobial Properties ◽  
Helical Structure ◽  
Peptide Backbone ◽  
Parent Molecule

ABSTRACT Endogenous antimicrobial peptides of the cathelicidin family contribute to innate immunity. The emergence of widespread antibiotic resistance in many commonly encountered bacteria requires the search for new bactericidal agents with therapeutic potential. Solid-phase synthesis was employed to prepare linear antimicrobial peptides found in cathelicidins of five mammals: human (FALL39/LL37), rabbit (CAP18), mouse (mCRAMP), rat (rCRAMP), and sheep (SMAP29 and SMAP34). These peptides were tested at ionic strengths of 25 and 175 mM against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Each peptide manifested activity against P. aeruginosa irrespective of the NaCl concentration. CAP18 and SMAP29 were the most effective peptides of the group against all test organisms under both low- and high-salt conditions. Select peptides of 15 to 21 residues, modeled on CAP18 (37 residues), retained activity against the gram-negative bacteria and methicillin-sensitive S. aureus, although the bactericidal activity was reduced compared to that of the parent peptide. In accordance with the behavior of the parent molecule, the truncated peptides adopted an α-helical structure in the presence of trifluoroethanol or lipopolysaccharide. The relationship between the bactericidal activity and several physiochemical properties of the cathelicidins was examined. The activities of the full-length peptides correlated positively with a predicted gradient of hydrophobicity along the peptide backbone and with net positive charge; they correlated inversely with relative abundance of anionic residues. The salt-resistant, antimicrobial properties of CAP18 and SMAP29 suggest that these peptides or congeneric structures have potential for the treatment of bacterial infections in normal and immunocompromised persons and individuals with cystic fibrosis.

scholarly journals Enhanced Antimicrobial Activity of N-Terminal Derivatives of a Novel Brevinin-1 Peptide from The Skin Secretion of Odorrana schmackeri

Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 484 ◽  
Author(s):  
Xiaowei Zhou ◽  
Yue Liu ◽  
Yitian Gao ◽  
Yuanxing Wang ◽  
Qiang Xia ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Antimicrobial Activity ◽  
Bacterial Infections ◽  
Therapeutic Index ◽  
Skin Secretion ◽  
Amphibian Skin ◽  
Transmission Electron ◽  
Conventional Antibiotics ◽  
Therapeutic Alternatives ◽  
Promising Source

Antimicrobial peptides (AMPs) are promising therapeutic alternatives compared to conventional antibiotics for the treatment of drug-resistant bacterial infections. However, the application of the overwhelming majority of AMPs is limited because of the high toxicity and high manufacturing costs. Amphibian skin secretion has been proven to be a promising source for the discovery and development of novel AMPs. Herein, we discovered a novel AMP from the skin secretion of Odorrana schmackeri, and designed the analogues by altering the key factors, including conformation, net charge and amphipathicity, to generate short AMPs with enhanced therapeutic efficacy. All the peptides were chemically synthesised, followed by evaluating their biological activity, stability and cytotoxicity. OSd, OSe and OSf exhibited broad-spectrum antibacterial effects, especially OSf, which presented the highest therapeutic index for the tested bacteria. Moreover, these peptides displayed good stability. The results from scanning electron microscopy and transmission electron microscopy studies, indicated that brevinin-OS, OSd, OSe and OSf possessed rapid bactericidal ability by disturbing membrane permeability and causing the release of cytoplasmic contents. In addition, OSd, OSe and OSf dramatically decreased the mortality of waxworms acutely infected with MRSA. Taken together, these data suggested that a balance between positive charge, degrees of α-helicity and hydrophobicity, is necessary for maintaining antimicrobial activity, and these data successfully contributed to the design of short AMPs with significant bactericidal activity and cell selectivity.

scholarly journals Human Antimicrobial Peptides as Therapeutics for Viral Infections

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 704 ◽  
Author(s):  
Aslaa Ahmed ◽  
Gavriella Siman-Tov ◽  
Grant Hall ◽  
Nishank Bhalla ◽  
Aarthi Narayanan
Keyword(s):  
Antimicrobial Peptides ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Antimicrobial Activities ◽  
Viral Pathogens ◽  
Multiple Organs ◽  
Pathogen Entry ◽  
Primary Focus ◽  
Therapeutic Tools

Successful in vivo infection following pathogen entry requires the evasion and subversion of multiple immunological barriers. Antimicrobial peptides (AMPs) are one of the first immune pathways upregulated during infection by multiple pathogens, in multiple organs in vivo. In humans, there are many classes of AMPs exhibiting broad antimicrobial activities, with defensins and the human cathelicidin LL-37 being the best studied examples. Whereas historically the efficacy and therapeutic potential of AMPs against bacterial infection has been the primary focus of research, recent studies have begun to elucidate the antiviral properties of AMPs as well as their role in regulation of inflammation and chemoattraction. AMPs as therapeutic tools seem especially promising against emerging infectious viral pathogens for which no approved vaccines or treatments are currently available, such as dengue virus (DENV) and Zika virus (ZIKV). In this review, we summarize recent studies elucidating the efficacy and diverse mechanisms of action of various classes of AMPs against multiple viral pathogens, as well as the potential use of human AMPs in novel antiviral therapeutic strategies.

scholarly journals Extracellular Vesicle Quantification and Characterization: Common Methods and Emerging Approaches

2019 ◽  
Vol 6 (1) ◽  
pp. 7 ◽  
Author(s):  
Thomas Hartjes ◽  
Serhii Mytnyk ◽  
Guido Jenster ◽  
Volkert van Steijn ◽  
Martin van Royen
Keyword(s):  
Physical Properties ◽  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Therapeutic Potential ◽  
Membrane Vesicles ◽  
Extracellular Vesicle ◽  
Medical Applications ◽  
Accurate Assessment ◽  
Further Development

Extracellular vesicles (EVs) are a family of small membrane vesicles that carry information about cells by which they are secreted. Growing interest in the role of EVs in intercellular communication, but also in using their diagnostic, prognostic and therapeutic potential in (bio) medical applications, demands for accurate assessment of their biochemical and physical properties. In this review, we provide an overview of available technologies for EV analysis by describing their working principles, assessing their utility in EV research and summarising their potential and limitations. To emphasise the innovations in EV analysis, we also highlight the unique possibilities of emerging technologies with high potential for further development.

Fundamental Studies of Bacterial Leaching Using Bio-Physical Techniques of Transmission Electron Microscopy

1975 ◽  
Vol 33 ◽  
pp. 644-645
Author(s):  
V.K. Berry ◽  
L.E. Murr
Keyword(s):  
Bacterial Attachment ◽  
Water Soluble ◽  
Metal Sulfides ◽  
Bacterial Leaching ◽  
Research Areas ◽  
Transmission Electron ◽  
Further Development ◽  
Soluble Sulfates ◽  
Metallurgical Processes

The role of microorganisms and their reaction with minerals are comparatively newer research areas in the general area of chemical mining, and have considerable scope of further development. The most commonly studied reactions of this type have been associated with microorganisms characterized as Thiobacillus thio-oxidans and Thiobacillus ferroxidans. These microorganisms have the ability to oxidize heavy metal sulfides and elemental sulfur to water soluble sulfates; and ferrous iron to ferric iron.The attachment location of biological microorganisms on minerals has not been reported in the literature as it relates specifically to biogenic metallurgical processes, although an attempt to describe the mode and character of bacterial attachment has been made by some workers. In the current investigation, a thermophillic microbe previously described by Brierley and Brierley and suggested to have a relationship with Sulfolobus was used. This microorganism exhibits an intracellular retractile body un-like Sulfolobus.

scholarly journals The Analogs of Temporin-GHa Exhibit a Broader Spectrum of Antimicrobial Activity and a Stronger Antibiofilm Potential against Staphylococcus aureus

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4173 ◽  
Author(s):  
Zhipeng Xie ◽  
Hanqi Wei ◽  
Jiahui Meng ◽  
Tong Cheng ◽  
Yanting Song ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Therapeutic Potential ◽  
Membrane Damage ◽  
Therapeutic Index ◽  
Antibacterial Activities ◽  
Therapeutic Window ◽  
Resistant Bacteria ◽  
Cell Selectivity ◽  
Initial Adhesion

The abuse of antibiotics has led to the emergence of multidrug-resistant bacteria, which is becoming a serious worldwide problem people have to face. In our previous study, temporin-GHa (GHa) cloned from Hylarana guentheri showed antimicrobial activity against Gram-positive bacteria. In order to improve its therapeutic potential, we used a template-based and a database-assisted design to obtain three derived peptides by replacing the histidine at both ends of GHa with lysine, which exhibited faster and stronger bactericidal activity and a broader spectrum than the parent peptide. GHaK and GHa4K targeted to the bacterial membrane to exert their antibacterial activities at a faster membrane damage rate. The derived peptides inhibited the initial adhesion and the formation of Staphylococcus aureus biofilms, and eradicated the mature biofilms, which indicated that the derived peptides effectively penetrated the biofilm and killed bacteria. The therapeutic index (TI) and cell selectivity index (CSI) of the derived peptides increased significantly, which means a broader therapeutic window of the derived peptides. The derived peptides with improved activity and cell selectivity have the potential to be the promising candidates for the treatment of S. aureus infections. Our research also provides new insights into the design and development of antimicrobial peptides.

Sign in / Sign up

Export Citation Format

Share Document