scholarly journals Multitalented Synthetic Antimicrobial Peptides and Their Antibacterial, Antifungal and Antiviral Mechanisms

2022 ◽  
Vol 23 (1) ◽  
pp. 545
Author(s):  
Tania Vanzolini ◽  
Michela Bruschi ◽  
Andrea C. Rinaldi ◽  
Mauro Magnani ◽  
Alessandra Fraternale
Keyword(s):  
Antimicrobial Peptides ◽  
Fungal Infections ◽  
Protein Biosynthesis ◽  
Cell Interaction ◽  
Resistant Bacteria ◽  
Emerging Infections ◽  
Fungal Cell ◽  
Viral Receptor ◽  
Promising Tool ◽  
Antibacterial And Antifungal

Despite the great strides in healthcare during the last century, some challenges still remained unanswered. The development of multi-drug resistant bacteria, the alarming growth of fungal infections, the emerging/re-emerging of viral diseases are yet a worldwide threat. Since the discovery of natural antimicrobial peptides able to broadly hit several pathogens, peptide-based therapeutics have been under the lenses of the researchers. This review aims to focus on synthetic peptides and elucidate their multifaceted mechanisms of action as antiviral, antibacterial and antifungal agents. Antimicrobial peptides generally affect highly preserved structures, e.g., the phospholipid membrane via pore formation or other constitutive targets like peptidoglycans in Gram-negative and Gram-positive bacteria, and glucan in the fungal cell wall. Additionally, some peptides are particularly active on biofilm destabilizing the microbial communities. They can also act intracellularly, e.g., on protein biosynthesis or DNA replication. Their intracellular properties are extended upon viral infection since peptides can influence several steps along the virus life cycle starting from viral receptor-cell interaction to the budding. Besides their mode of action, improvements in manufacturing to increase their half-life and performances are also taken into consideration together with advantages and impairments in the clinical usage. Thus far, the progress of new synthetic peptide-based approaches is making them a promising tool to counteract emerging infections.

Gingerol Derivatives as 14α-demethylase Inhibitors: Design and Development of Natural, Safe Antifungals for Immune-compromised Patients

2020 ◽  
Vol 17 (7) ◽  
pp. 918-928
Author(s):  
Sweta Sharma ◽  
Arpita Yadav
Keyword(s):  
Cell Membranes ◽  
Fungal Infections ◽  
Dynamics Simulation ◽  
Stable Complex ◽  
Active Site Residues ◽  
Design And Development ◽  
Triazole Derivative ◽  
Fungal Cell ◽  
Term Administration ◽  
Compromised Patients

Background: : Currently, clinically used drugs for internal fungal infections have severe side effects. Patients suffering from severe fungal infections and those at a constant risk of developing such infections require long-term administration of safe antifungals. Objective: : This work deals with the design and development of safe, non-toxic antifungals derived from natural compounds for immune-compromised patients, such as HIV patients, who are at a constant risk of developing internal fungal infections. Methods: : Molecular modeling, docking and molecular dynamics simulation studies were performed on the main constituents of ginger and their derivatives to study their capability to inhibit 14α- demethylase enzyme. Results: : Ergosterol is the key component of the fungal cell membrane for its integrity and rigidity, synthesized from lanosterol catalyzed by 14α-demethylase enzyme. In our studies, it is determined that 6-gingerol, 6-paradol, 6-shogaol and their imidazole and triazole derivatives can inhibit the synthesis of ergosterol thus weakening the fungal cell membranes. The triazole derivative of 6-gingerol forms enhanced binding interactions with the active site residues of 14α-demethylase, carries an affinity for catalytically required cofactor heme and forms a stable complex with time without the probability of premature expulsion. Thus, this compound inhibits the formation of ergosterol leading to weakened fungal cell membranes and eventually death of fungal cells. Conclusion: : The triazole derivative of 6-gingerol is recommended as a lead compound for the development of non-toxic antifungals.

scholarly journals Protein-Engineered Polymers Functionalized with Antimicrobial Peptides for the Development of Active Surfaces

2021 ◽  
Vol 11 (12) ◽  
pp. 5352
Author(s):  
Ana Margarida Pereira ◽  
Diana Gomes ◽  
André da Costa ◽  
Simoni Campos Dias ◽  
Margarida Casal ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptides ◽  
Recombinant Dna ◽  
Biological Properties ◽  
Resistant Bacteria ◽  
Recombinant Dna Technology ◽  
Free Standing ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Antimicrobial Materials

Antibacterial resistance is a major worldwide threat due to the increasing number of infections caused by antibiotic-resistant bacteria with medical devices being a major source of these infections. This suggests the need for new antimicrobial biomaterial designs able to withstand the increasing pressure of antimicrobial resistance. Recombinant protein polymers (rPPs) are an emerging class of nature-inspired biopolymers with unique chemical, physical and biological properties. These polymers can be functionalized with antimicrobial molecules utilizing recombinant DNA technology and then produced in microbial cell factories. In this work, we report the functionalization of rPBPs based on elastin and silk-elastin with different antimicrobial peptides (AMPs). These polymers were produced in Escherichia coli, successfully purified by employing non-chromatographic processes, and used for the production of free-standing films. The antimicrobial activity of the materials was evaluated against Gram-positive and Gram-negative bacteria, and results showed that the polymers demonstrated antimicrobial activity, pointing out the potential of these biopolymers for the development of new advanced antimicrobial materials.

scholarly journals The Lactococcal dgkB (yecE) and dxsA Genes for Lipid Metabolism Are Involved in the Resistance to Cell Envelope-Acting Antimicrobials

2021 ◽  
Vol 22 (3) ◽  
pp. 1014
Author(s):  
Aleksandra Tymoszewska ◽  
Tamara Aleksandrzak-Piekarczyk
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Cytoplasmic Membrane ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
Membrane Targeting ◽  
Nucleotide Polymorphisms ◽  
Next Generation ◽  
Lipid Ii

The emergence of antibiotic-resistant bacteria led to an urgent need for next-generation antimicrobial agents with novel mechanisms of action. The use of positively charged antimicrobial peptides that target cytoplasmic membrane is an especially promising strategy since essential functions and the conserved structure of the membrane hinder the development of bacterial resistance. Aureocin A53- and enterocin L50-like bacteriocins are highly cationic, membrane-targeting antimicrobial peptides that have potential as next-generation antibiotics. However, the mechanisms of resistance to these bacteriocins and cross-resistance against antibiotics must be examined before application to ensure their safe use. Here, in the model bacterium Lactococcus lactis, we studied the development of resistance to selected aureocin A53- and enterocin L50-like bacteriocins and its correlation with antibiotics. First, to generate spontaneous resistant mutants, L.lactis was exposed to bacteriocin BHT-B. Sequencing of their genomes revealed single nucleotide polymorphisms (SNPs) in the dgkB (yecE) and dxsA genes encoding diacylglycerol kinase and 1-deoxy-D-xylulose 5-phosphate synthase, respectively. Then, selected mutants underwent susceptibility tests with a wide array of bacteriocins and antibiotics. The highest alterations in the sensitivity of studied mutants were seen in the presence of cytoplasmic membrane targeting bacteriocins (K411, Ent7, EntL50, WelM, SalC, nisin) and antibiotics (daptomycin and gramicidin) as well as lipid II cycle-blocking bacteriocins (nisin and Lcn972) and antibiotics (bacitracin). Interestingly, decreased via the SNPs accumulation sensitivity to membrane-active bacteriocins and antibiotics resulted in the concurrently increased vulnerability to bacitracin, carbenicillin, or chlortetracycline. It is suspected that SNPs may result in alterations to the efficiency of the nascent enzymes rather than a total loss of their function as neither deletion nor overexpression of dxsA restored the phenotype observed in spontaneous mutants.

scholarly journals Spatial Distribution of a Porphyrin-Based Photosensitizer Reveals Mechanism of Photodynamic Inactivation of Candida albicans

2021 ◽  
Vol 8 ◽  
Author(s):  
Thomas Voit ◽  
Fabian Cieplik ◽  
Johannes Regensburger ◽  
Karl-Anton Hiller ◽  
Anita Gollmer ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fungal Infections ◽  
Cell Envelope ◽  
Antimicrobial Photodynamic Therapy ◽  
Fungal Cell ◽  
Before And After ◽  
Antifungal Action ◽  
Complete Cell ◽  
Further Development

The antimicrobial photodynamic therapy (aPDT) is a promising approach for the control of microbial and especially fungal infections such as mucosal mycosis. TMPyP [5,10,15, 20-tetrakis(1-methylpyridinium-4-yl)-porphyrin tetra p-toluenesulfonate] is an effective photosensitizer (PS) that is commonly used in aPDT. The aim of this study was to examine the localization of TMPyP in Candida albicans before and after irradiation with visible light to get information about the cellular mechanism of antifungal action of the photodynamic process using this PS. Immediately after incubation of C. albicans with TMPyP, fluorescence microscopy revealed an accumulation of the PS in the cell envelope. After irradiation with blue light the complete cell showed red fluorescence, which indicates, that aPDT is leading to a damage in the cell wall with following influx of PS into the cytosol. Incubation of C. albicans with Wheat Germ Agglutinin (WGA) could confirm the cell wall as primary binding site of TMPyP. The finding that the porphyrin accumulates in the fungal cell wall and does not enter the interior of the cell before irradiation makes it unlikely that resistances can emerge upon aPDT. The results of this study may help in further development and modification of PS in order to increase efficacy against fungal infections such as those caused by C. albicans.

scholarly journals Nanoparticles Enable Efficient Delivery of Antimicrobial Peptides for the Treatment of Deep Infections

2021 ◽  
Author(s):  
Yingxue Deng ◽  
Rui Huang ◽  
Songyin Huang ◽  
Menghua Xiong
Keyword(s):  
Antimicrobial Peptides ◽  
Broad Spectrum ◽  
Antimicrobial Properties ◽  
Therapeutic Index ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Efficient Delivery ◽  
Delivery Vehicles

Antimicrobial peptides (AMPs) have emerged as promising alternatives of traditional antibiotics against drug-resistant bacteria owing to their broad-spectrum antimicrobial properties and low tendency to drugresistance. However, their therapeutic efficacy in vivo, especially for infections in deep organs, is limited owing to their systemic toxicity and low bioavailability. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Herein, we will discuss the current progress of using nanoparticles as delivery vehicles for AMPs for the treatment of deep infections.

Rapid determination of binding parameters of chitin binding domains using chitin-coated quartz crystal microbalance sensor chips

The Analyst ◽  
2018 ◽  
Vol 143 (21) ◽  
pp. 5255-5263 ◽  
Author(s):  
Stephan Vogt ◽  
Marco Kelkenberg ◽  
Tanja Nöll ◽  
Benedikt Steinhoff ◽  
Holger Schönherr ◽  
...  
Keyword(s):  
Cell Walls ◽  
Quartz Crystal ◽  
Fungal Infections ◽  
Rapid Determination ◽  
Binding Parameters ◽  
Fungal Cell ◽  
Binding Domains ◽  
Quartz Crystal Microbalance Sensor ◽  
Fungal Cell Walls

Chitin present in fungal cell walls has been considered as a diagnostic polymer for the detection of fungal infections.

Molecular Modeling Study for the Evaluation of Natural Compounds as Potential Lanosterol 14α-demethylase Inhibitors

2021 ◽  
Vol 18 ◽  
Author(s):  
Nidhi Rani ◽  
Randhir Singh ◽  
Praveen Kumar
Keyword(s):  
Molecular Docking ◽  
Molecular Modeling ◽  
Fungal Infections ◽  
Docking Study ◽  
Natural Compounds ◽  
Docking Studies ◽  
Prosthetic Group ◽  
Fungal Cell ◽  
Adme Profile ◽  
Target Enzyme

Background: Candida albicans is one of the most important causes of fatal fungal infections. Ergosterol, the main sterol in the fungal cell membrane, is the resultant product of Lanosterol in the presence of the enzyme Lanosterolα-demethylase (Cytochrome P450DM). This enzyme is the target enzyme of azole antifungal agents. Aim: To evaluate the antifungal potency of some of the natural compounds via molecular modeling and Absorption, Distribution, Metabolism and Excretion (ADME) study. Method: The study involved the selection and modeling of the target enzyme, followed by the refinement of the model using molecular dynamic simulation. The modelled structure of the enzyme was validated using the Ramachandran plot and Sequence determination technique. A series of natural compounds was evaluated for cytochrome P450 inhibitory activity using molecular docking studies. The structures of compounds were prepared using a Chem sketch, and molecular docking was performed using Molergo Virtual Docker (MVD) program. Results: The docking study indicated that all the natural compounds have interactivity with protein residue of 14α-demethylase, and the heme prosthetic group and water molecules are present at the active site. The data were also correlated with the synthetic compounds that were experimentally inactive against the fungus and had a low docking score. The compounds with a high dock score were further screened for Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profile, and it was predicted that these compounds can be used as lead with a good ADME profile and low toxicity. Conclusion: The natural compound, i.e., curcumin, can easily be used further for lead optimization.

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