Antimicrobial Activity of Small β-Peptidomimetics Based on the Pharmacophore Model of Short Cationic Antimicrobial Peptides

BACKGROUND Cationic antimicrobial peptides have broad antimicrobial activity and provide a novel way of targeting multi drug resistant bacteria in an era of increasing antimicrobial resistance. Current developments show positive prospects for both antimicrobial peptides and silver nanoparticles individually. OBJECTIVE The primary objective is to propose another method of enhancing antimicrobial activity by conjugating silver nanoparticles with cationic antimicrobial peptides for a subsequent preliminary assessment on studying the minimum inhibitory concentration of multi drug resistant bacteria. The secondary objective would be to evaluate the safety of the conjugated compound to assess viability for in vivo use. METHODS The proposition is planned for approximately 3 overarching stages. Firstly, I propose synthesis of wlbu2c, a modified version of antimicrobial peptide wlbu2 with an added cysteine group, using standard Fmoc procedure. This will subsequently be attempted to stably conjugate with silver nanoparticles ideally through photochemical means. Secondly, the conjugate wlbu2c-AgNP will be tested for antimicrobial activity following Clinical & Laboratory Standards Institute Manual on standard minimum inhibitory concentration testing. If all of the above is completed the experiment can progress to the assessment of cytotoxicity using cell lysis assays. RESULTS I-TASSER simulation revealed that our modified peptide wlbu2c has similar secondary structure to original wlbu2 peptide. No other results have been obtained at this time other than aforementioned theoretical propositions. CONCLUSIONS The addition of silver nanoparticles to already developing de novo engineered antimicrobial peptides provide a second degree of freedom toward the development of potent antimicrobials. Future prospects include emergency last line therapy, treatment for current difficult to eradicate bacterial colonization such as in cystic fibrosis, implantable medical devices, cancer and immunotherapy. This proposal is intended to be provided to the public as I do not anticipate funding at this time.

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Antimicrobial Activity of Cationic Antimicrobial Peptides against Gram-Positives: Current Progress Made in Understanding the Mode of Action and the Response of Bacteria

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2016.00111 ◽

2016 ◽

Vol 4 ◽

Cited By ~ 61

Author(s):

Soraya Omardien ◽

Stanley Brul ◽

Sebastian A. J. Zaat

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Mode Of Action ◽

Cationic Antimicrobial Peptides ◽

Made In

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Faculty Opinions recommendation of Role of the LytSR two-component regulatory system in adaptation to cationic antimicrobial peptides in Staphylococcus aureus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718023499.793479411 ◽

2013 ◽

Author(s):

Suzanne Walker ◽

Mithila Rajagopal

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Peptides ◽

Regulatory System ◽

Cationic Antimicrobial Peptides ◽

Two Component

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Faculty Opinions recommendation of Small cationic antimicrobial peptides delocalize peripheral membrane proteins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718339795.793494873 ◽

2014 ◽

Author(s):

Stanley Brul

Keyword(s):

Membrane Proteins ◽

Antimicrobial Peptides ◽

Cationic Antimicrobial Peptides ◽

Peripheral Membrane Proteins

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Cationic Antimicrobial Peptides for Tuberculosis: A Mini-Review

Current Protein and Peptide Science ◽

10.2174/1389203720666190626160057 ◽

2019 ◽

Vol 20 (9) ◽

pp. 885-892

Author(s):

Sara Silva ◽

Nuno Vale

Keyword(s):

Mycobacterium Tuberculosis ◽

Amino Acid ◽

Antimicrobial Peptides ◽

Resistance Mechanisms ◽

Therapeutic Agents ◽

Pharmacological Properties ◽

Therapeutic Activity ◽

Alternative Strategies ◽

Cationic Antimicrobial Peptides ◽

Specific Amino Acid

Cationic antimicrobial peptides (CAMPs) can be considered as new potential therapeutic agents for Tuberculosis treatment with a specific amino acid sequence. New studies can be developed in the future to improve the pharmacological properties of CAMPs and also understand possible resistance mechanisms. This review discusses the principal properties of natural and/or synthetic CAMPs, and how these new peptides have a significant specificity for Mycobacterium tuberculosis. Also, we propose some alternative strategies to enhance the therapeutic activity of these CAMPs that include coadministration with nanoparticles and/or classic drugs.

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Plant antimicrobial peptides: structures, functions, and applications

Botanical Studies ◽

10.1186/s40529-021-00312-x ◽

2021 ◽

Vol 62 (1) ◽

Author(s):

Junpeng Li ◽

Shuping Hu ◽

Wei Jian ◽

Chengjian Xie ◽

Xingyong Yang

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Agricultural Production ◽

Food Additives ◽

Antimicrobial Activities ◽

Gram Positive Bacteria ◽

Potential Applications ◽

Potential Applicability ◽

Bacteria And Fungi ◽

Positively Charged

AbstractAntimicrobial peptides (AMPs) are a class of short, usually positively charged polypeptides that exist in humans, animals, and plants. Considering the increasing number of drug-resistant pathogens, the antimicrobial activity of AMPs has attracted much attention. AMPs with broad-spectrum antimicrobial activity against many gram-positive bacteria, gram-negative bacteria, and fungi are an important defensive barrier against pathogens for many organisms. With continuing research, many other physiological functions of plant AMPs have been found in addition to their antimicrobial roles, such as regulating plant growth and development and treating many diseases with high efficacy. The potential applicability of plant AMPs in agricultural production, as food additives and disease treatments, has garnered much interest. This review focuses on the types of plant AMPs, their mechanisms of action, the parameters affecting the antimicrobial activities of AMPs, and their potential applications in agricultural production, the food industry, breeding industry, and medical field.

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The effect of structural modification of antimicrobial peptides on their antimicrobial activity, hemolytic activity, and plasma stability

Journal of Peptide Science ◽

10.1002/psc.3306 ◽

2021 ◽

Author(s):

Taoran Wang ◽

Cunbin Zou ◽

Na Wen ◽

Xingdong Liu ◽

Zhao Meng ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Hemolytic Activity ◽

Structural Modification ◽

Plasma Stability

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

Applied Sciences ◽

10.3390/app11125352 ◽

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.

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