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Unlocking the Power of Peptide-Based Anti-Antimicrobial Agents: A Game-Changer in Fighting Bacterial Infections

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Overview of Peptide-Based Anti-Antimicrobial Agents

Peptide-based antimicrobial agents have emerged as a promising alternative to traditional antimicrobial treatments for microbial infections. These agents are short chains of amino acids that can kill or inhibit the growth of various types of microbes, including bacteria, fungi, and viruses. They work by targeting specific components of microbial cells, such as cell membranes or intracellular proteins, disrupting their structure and function. This article will provide an in-depth analysis of the mechanisms of action of peptide-based antimicrobial agents and their potential applications in treating microbial infections.

Mechanisms of Action of Peptide-Based Antimicrobial Agents

Peptide-based antimicrobial agents exert their activity through multiple mechanisms, making them effective against a wide range of pathogens. Some common mechanisms include:

1. Disruption of cell membranes: Many peptide-based agents have a positive charge and can interact with negatively charged components on the surface of microbial cells. This interaction disrupts the integrity of the cell membrane, leading to leakage of cellular contents and ultimately cell death.

2. Inhibition of protein synthesis: Certain peptides can interfere with essential cellular processes by binding to ribosomes or other protein synthesis machinery within microbial cells. This disruption prevents the production of vital proteins necessary for microbial survival.

3. Targeting intracellular components: Some peptide-based agents can penetrate into microbial cells and target specific intracellular components, such as DNA or enzymes involved in replication or metabolism. By interfering with these essential processes, they effectively inhibit the growth and proliferation of microbes.

4. Modulation of immune response: Peptides derived from natural host defense proteins can also modulate the immune response against microbial infections. They can enhance the activity of immune cells, such as neutrophils or macrophages, promoting clearance of pathogens.

Comparative Analysis: Peptide-Based Agents vs. Traditional Antimicrobial Treatments

Peptide-based antimicrobial agents offer several advantages over traditional antimicrobial treatments. Some key points of comparison include:

1. Broad-spectrum activity: Peptide-based agents have demonstrated efficacy against a wide range of pathogens, including drug-resistant strains. This broad-spectrum activity makes them particularly valuable in the era of increasing antibiotic resistance.

2. Lower propensity for resistance development: Due to their complex mechanisms of action and multiple targets within microbial cells, peptide-based agents have a lower likelihood of developing resistance compared to traditional antibiotics. This is a significant advantage in combating multidrug-resistant infections.

3. Rapid killing kinetics: Peptide-based agents often exhibit rapid bactericidal or fungicidal activity, leading to more rapid clearance of infections. This can be particularly beneficial in severe or life-threatening infections where prompt treatment is crucial.

4. Potential for synergy with existing treatments: Peptide-based agents can also be used in combination with traditional antimicrobial treatments to enhance their effectiveness or overcome resistance mechanisms. This synergistic approach holds promise for improving treatment outcomes and reducing the risk of treatment failure.

Overall, peptide-based antimicrobial agents represent a promising class of therapeutics that can address the growing challenges posed by microbial infections and antibiotic resistance. Their unique mechanisms of action, broad-spectrum activity, and potential for synergy with existing treatments make them an attractive option for future therapeutic development.

Mechanisms of Action of Peptide-Based Antimicrobial Agents

Peptide Structure and Function

Peptide-based antimicrobial agents are small chains of amino acids that possess unique structural features and functional properties. These peptides typically consist of 10 to 50 amino acids and can adopt various secondary structures, such as alpha-helices, beta-sheets, or extended loops. The specific arrangement of these amino acids allows peptides to interact with microbial membranes or intracellular targets, leading to their antimicrobial activity. The cationic nature of many peptide-based agents enables them to selectively bind to negatively charged components on the surface of bacteria, fungi, or viruses.

Membrane Disruption Mechanisms

One key mechanism by which peptide-based antimicrobial agents exert their action is through membrane disruption. These peptides can insert themselves into the lipid bilayer of microbial membranes, causing destabilization and permeabilization. This disruption leads to the leakage of cellular contents and ultimately cell death. Additionally, some peptides can form pores in the membrane, further compromising its integrity and allowing for increased influx of ions and other molecules.

Intracellular Targeting Mechanisms

In addition to membrane disruption, peptide-based agents can also target intracellular components within microbial cells. These peptides may interact with vital cellular structures such as DNA, RNA, or proteins, disrupting their normal functions and inhibiting essential processes required for microbial survival. By targeting multiple intracellular sites simultaneously, peptide-based agents can effectively prevent the development of resistance mechanisms.

Overall, the mechanisms of action employed by peptide-based antimicrobial agents involve a combination of membrane disruption and intracellular targeting. Their ability to interact with both extracellular and intracellular components makes them potent against a wide range of pathogens while minimizing the likelihood of resistance development.

Comparative Analysis: Peptide-Based Agents vs. Traditional Antimicrobial Treatments

Efficacy and Spectrum of Activity

When comparing peptide-based antimicrobial agents to traditional antimicrobial treatments, several factors come into play. One important aspect is their efficacy and spectrum of activity. Peptide-based agents have demonstrated broad-spectrum antimicrobial activity against various pathogens, including bacteria, fungi, and viruses. They can effectively target both Gram-positive and Gram-negative bacteria, making them versatile in combating different types of infections.

Resistance Development

Another crucial consideration is the development of resistance. Traditional antimicrobial treatments often face challenges due to the emergence of resistant strains. However, peptide-based agents have shown a lower propensity for resistance development compared to conventional antibiotics. This is primarily attributed to their multifaceted mechanisms of action, which make it difficult for pathogens to develop specific resistance mechanisms against them.

Host Immune Response

Peptide-based agents also interact with the host immune system in unique ways compared to traditional antimicrobials. These peptides can modulate immune responses by enhancing the recruitment and activation of immune cells, promoting wound healing processes, and reducing inflammation at the site of infection. This immunomodulatory effect contributes to the overall effectiveness of peptide-based agents in combating infections.

peptide-based antimicrobial agents offer distinct advantages over traditional treatments in terms of their broad-spectrum activity, reduced likelihood of resistance development, and ability to modulate host immune responses. These characteristics make them promising candidates for addressing the growing challenge of antimicrobial resistance.

Efficacy Studies: Assessing the Effectiveness of Peptide-Based Antimicrobial Agents

In vitro Studies

Evaluating the efficacy of peptide-based antimicrobial agents involves conducting comprehensive studies that assess their effectiveness against various pathogens. In vitro studies are commonly performed as a first step to determine the antimicrobial activity of these agents. These studies involve exposing microbial cultures to different concentrations of peptide-based agents and measuring their inhibitory or bactericidal effects.

Minimum Inhibitory Concentration (MIC)

One commonly used parameter in in vitro efficacy studies is the determination of the minimum inhibitory concentration (MIC). The MIC represents the lowest concentration of a peptide-based agent that prevents visible growth of a microorganism. This measurement provides valuable information about the potency and effectiveness of the agent against specific pathogens.

Time-Kill Assays

Time-kill assays are another important tool for assessing the efficacy of peptide-based antimicrobial agents. These assays involve exposing microbial cultures to a fixed concentration of the agent over a specified period and periodically sampling to determine bacterial viability. By monitoring bacterial growth or killing kinetics, researchers can gain insights into the speed and extent of antimicrobial activity exhibited by these agents.

In vivo Studies

While in vitro studies provide valuable preliminary data, it is essential to evaluate the efficacy of peptide-based antimicrobial agents in more complex biological systems. In vivo studies involving animal models are conducted to assess factors such as pharmacokinetics, tissue distribution, and overall therapeutic efficacy. These studies help bridge the gap between laboratory experiments and potential clinical applications.

evaluating the efficacy of peptide-based antimicrobial agents requires a comprehensive approach involving both in vitro and in vivo studies. These investigations provide crucial insights into their potency, mechanism of action, and potential therapeutic applications against various pathogens.

Challenges and Limitations in Developing Peptide-Based Antimicrobial Agents

Peptide Stability

One significant challenge in developing peptide-based antimicrobial agents lies in ensuring their stability under physiological conditions. Peptides are susceptible to degradation by proteases present in biological fluids, which can limit their effectiveness when administered systemically. Strategies such as chemical modifications or encapsulation in nanoparticles have been explored to enhance peptide stability and prolong their activity.

Cost of Production

Another limitation is the cost associated with large-scale production of peptide-based agents. Peptides are typically synthesized through solid-phase peptide synthesis, which can be time-consuming and expensive. The high manufacturing costs may hinder the widespread use and accessibility of these agents, particularly in resource-limited settings.

Specificity and Selectivity

Achieving specificity and selectivity against pathogens while minimizing off-target effects on host cells is a crucial challenge in developing peptide-based antimicrobial agents. Designing peptides that selectively target microbial membranes or intracellular components without affecting mammalian cells requires careful consideration of their physicochemical properties and interactions with different cellular components.

the development of peptide-based antimicrobial agents faces challenges related to stability, production costs, and achieving optimal specificity and selectivity. Overcoming these limitations will require innovative approaches and collaborations between researchers from various disciplines to harness the full potential of these promising therapeutic agents.

Novel Approaches: Enhancing the Activity of Peptide-Based Antimicrobial Agents

Combination Therapies

To enhance the activity of peptide-based antimicrobial agents, researchers have explored combination therapies that involve using these peptides in conjunction with other antimicrobial agents or adjuvants. Combining peptides with traditional antibiotics or synergistic compounds can lead to enhanced efficacy by targeting multiple pathways or mechanisms within microbial cells.

Structural Modifications

Structural modifications of peptide-based agents offer another avenue for enhancing their activity. Alterations in amino acid sequence, introduction of non-natural amino acids, or incorporation of specific motifs can improve stability, increase binding affinity to microbial targets, or enhance membrane disruption capabilities. Rational design strategies coupled with computational modeling techniques play a crucial role in guiding these modifications.

Nanotechnology-Based Approaches

Nanotechnology has emerged as a promising field for enhancing the activity of peptide-based antimicrobial agents. Encapsulation of peptides within nanoparticles can protect them from degradation, improve their stability, and enable controlled release at the site of infection. Additionally, surface functionalization of nanoparticles with peptides can enhance their targeting capabilities and facilitate specific interactions with microbial cells.

novel approaches to enhancing the activity of peptide-based antimicrobial agents include combination therapies, structural modifications, and nanotechnology-based approaches. These strategies aim to overcome existing limitations and further optimize the therapeutic potential of peptide-based agents in combating microbial infections.

Safety Profile: Evaluating the Toxicity and Side Effects Associated with Peptide-Based Agents

Cellular Toxicity Studies

Assessing the safety profile of peptide-based antimicrobial agents involves evaluating their potential toxicity towards mammalian cells. Cellular toxicity studies are conducted to determine whether these agents exhibit any adverse effects on human or animal cells. Various assays measuring cell viability, membrane integrity, or metabolic activity provide insights into the cytotoxicity profile of these peptides.

Hemolytic Activity

One specific aspect of safety evaluation is assessing hemolytic activity. Hemolysis refers to the destruction of red blood cells, which can lead to severe complications if a therapeutic agent exhibits significant hemolytic properties. Peptide-based agents are tested for their ability to cause hemolysis using red blood cell lysis assays.

Animal Toxicity Studies

To further evaluate safety, animal toxicity studies are conducted using appropriate animal models. These studies assess potential systemic toxic effects such as organ toxicity, immunogenicity, or allergic reactions associated with peptide-based antimicrobial agents. Monitoring parameters such as body weight changes, histopathological analysis of tissues, or immune response markers provides valuable information on their safety profile.

evaluating the safety profile of peptide-based antimicrobial agents involves cellular toxicity studies, assessment of hemolytic activity, and animal toxicity studies. These investigations are crucial for ensuring the therapeutic potential of these agents while minimizing any potential harm to patients.

Clinical Applications: Current Use Cases for Peptide-Based Antimicrobial Agents

Topical Wound Care

One prominent clinical application of peptide-based antimicrobial agents is in topical wound care. Peptides with potent antimicrobial activity and immunomodulatory properties have been developed as topical formulations for treating infected wounds. These peptides can effectively target a wide range of pathogens commonly associated with wound infections, including antibiotic-resistant strains.

Respiratory Tract Infections

Peptide-based agents also show promise in the treatment of respiratory tract infections. Inhalation or intranasal administration of these peptides allows direct delivery to the site of infection, bypassing systemic circulation. This targeted approach enhances efficacy while minimizing potential side effects associated with systemic administration.

Catheter-Associated Infections

Catheter-associated infections pose a significant challenge in healthcare settings. Peptide-based antimicrobial coatings or impregnated catheters have been developed to prevent biofilm formation and reduce the risk of infection. These coatings release antimicrobial peptides locally, providing continuous protection against microbial colonization.

peptide-based antimicrobial agents find clinical applications in topical wound care, respiratory tract infections, and catheter-associated infections. Their broad-spectrum activity and ability to target specific sites make them valuable tools in combating various types of infections.

Preclinical and Clinical Development of Peptide-Based Antimicrobial Agents

Preclinical Studies

The preclinical development stage involves conducting extensive studies to evaluate the safety, efficacy, and pharmacokinetic properties of peptide-based antimicrobial agents. Preclinical studies typically include in vitro experiments, animal toxicity studies, and pharmacokinetic assessments. These investigations provide crucial data for selecting lead candidates and optimizing formulation strategies.

Formulation Development

During preclinical development, formulation strategies are explored to enhance the stability, bioavailability, and targeted delivery of peptide-based agents. Encapsulation in nanoparticles, liposomes, or hydrogels can protect peptides from degradation and enable controlled release at the site of infection. Formulation optimization ensures optimal therapeutic outcomes during subsequent clinical trials.

Regulatory Considerations

Preclinical development also involves addressing regulatory considerations to ensure compliance with safety and efficacy standards set by regulatory authorities. Data generated from preclinical studies are compiled into comprehensive reports that form the basis for seeking regulatory approvals to proceed with clinical trials.

Clinical Trials

Clinical trials are conducted to evaluate the safety and efficacy of peptide-based antimicrobial agents in humans. These trials follow a rigorous protocol involving different phases (Phase I-IV) to assess factors such as dosage, adverse effects, therapeutic effectiveness, and long-term outcomes.

Phase I: Safety Assessment

Phase I trials primarily focus on evaluating the safety profile of the peptide-based agent in a small group of healthy volunteers or patients. The main objective is to determine the maximum tolerated dose (MTD) and identify any potential adverse effects associated with different dosage levels.

Phase II: Efficacy Evaluation

Phase II trials involve a larger cohort of patients to assess the efficacy of the peptide-based agent against specific infections or indications. These trials aim to gather preliminary data on therapeutic effectiveness while continuing to monitor safety profiles.

Phase III: Confirmatory Studies

Phase III trials are large-scale studies conducted on a more diverse patient population to confirm the efficacy and safety observed in earlier phases. These trials provide robust evidence of the clinical benefits and establish the optimal dosage, administration route, and treatment duration.

the preclinical and clinical development of peptide-based antimicrobial agents involves extensive preclinical studies, formulation development, regulatory considerations, and well-designed clinical trials. These stages are essential for ensuring the safety, efficacy, and regulatory approval of these agents before they can be made available for widespread use.

Future Perspectives: Advancements and Potential Breakthroughs in Peptide-Based Antimicrobial Agents

Targeted Delivery Systems

Future advancements in peptide-based antimicrobial agents may involve the development of targeted delivery systems that enable precise delivery to specific sites of infection. Nanoparticles or other carrier systems can be engineered to selectively recognize and bind to microbial cells or infected tissues, enhancing therapeutic efficacy while minimizing off-target effects.

Combination Therapies with Immunomodulators

Combining peptide-based antimicrobial agents with immunomodulatory compounds represents another potential breakthrough. By simultaneously targeting pathogens and modulating immune responses, these combination therapies could enhance overall treatment outcomes by promoting more effective clearance of infections.

Engineering Resistance-Resistant Peptides

As resistance against traditional antibiotics continues to rise, future research may focus on engineering peptides that are less prone to resistance development. By designing peptides that target multiple essential pathways within microbial cells or developing strategies to prevent resistance mechanisms from emerging, researchers aim

Resistance Mechanisms: Understanding the Development of Resistance against Peptide-Based Agents

Mechanisms of Resistance

Peptide-based agents have shown great potential as antimicrobial agents, but their effectiveness can be limited by the development of resistance mechanisms. One common resistance mechanism is the modification or degradation of peptides by bacterial enzymes. These enzymes can cleave or modify the peptide structure, rendering it ineffective against the bacteria. Another mechanism involves changes in the bacterial cell membrane, which can prevent peptides from entering the cell or disrupt their interaction with intracellular targets. Additionally, bacteria can develop efflux pumps that actively pump out peptides before they can exert their antimicrobial effects. Understanding these resistance mechanisms is crucial for developing strategies to overcome them and enhance the efficacy of peptide-based agents.

Emergence and Spread of Resistance

The emergence and spread of resistance against peptide-based agents is a significant concern in the field of antimicrobial research. Bacteria have an incredible ability to adapt and evolve, allowing them to develop resistance mechanisms relatively quickly. This process is further facilitated by horizontal gene transfer, where bacteria can acquire resistance genes from other bacteria through plasmids or other mobile genetic elements. Once a resistant strain emerges, it has the potential to spread rapidly within a population or even between different species, posing a serious threat to public health. Monitoring and surveillance programs are essential for detecting and tracking the emergence and spread of resistance against peptide-based agents.

Strategies to Overcome Resistance

To combat resistance against peptide-based agents, researchers are exploring various strategies to enhance their effectiveness. One approach involves modifying existing peptides to make them less susceptible to enzymatic degradation or more potent against resistant strains. This could involve altering specific amino acids within the peptide sequence or incorporating non-natural amino acids with enhanced stability or activity. Another strategy focuses on combination therapy, where multiple peptides or peptide-based agents are used together to target different aspects of bacterial physiology and minimize the development of resistance. Additionally, researchers are investigating the use of adjuvants or enhancers that can potentiate the activity of peptides and overcome resistance mechanisms. These strategies hold promise in addressing the challenge of resistance against peptide-based agents.

Peptide-Based Agents for Multidrug-Resistant Infections: A Promising Solution?

The Rise of Multidrug-Resistant Infections

Multidrug-resistant infections have become a global health crisis, posing a significant challenge to healthcare systems worldwide. The overuse and misuse of conventional antibiotics have contributed to the emergence and spread of multidrug-resistant bacteria, making it difficult to treat infections effectively. Peptide-based agents offer a promising solution to combat these resistant pathogens due to their unique mechanism of action and broad-spectrum activity. Unlike traditional antibiotics, peptides can target multiple bacterial targets simultaneously, making it harder for bacteria to develop resistance against them. This makes peptide-based agents an attractive option for treating multidrug-resistant infections.

Efficacy Against Resistant Strains

One key advantage of peptide-based agents is their efficacy against resistant strains that are no longer responsive to conventional antibiotics. These resistant strains often possess various mechanisms that render them insensitive to traditional drugs, such as efflux pumps or altered cell membrane structures. However, peptides can bypass these resistance mechanisms by directly targeting essential bacterial components or disrupting vital cellular processes. Moreover, peptides have been shown to exhibit synergistic effects when combined with conventional antibiotics, enhancing their overall antimicrobial activity against multidrug-resistant strains. This combination therapy approach holds great promise in overcoming the challenges posed by multidrug-resistant infections.

Future Prospects and Challenges

While peptide-based agents show immense potential in combating multidrug-resistant infections, several challenges need to be addressed for their successful implementation. One major challenge is the development of resistance against peptides themselves. As with any antimicrobial agent, bacteria can potentially develop mechanisms to evade the activity of peptides, limiting their long-term efficacy. Additionally, the high cost of peptide production and limited stability in certain environments pose challenges for large-scale commercialization. Overcoming these obstacles will require continued research and development efforts, including the design of more stable and cost-effective peptide-based agents. Despite these challenges, peptide-based agents hold great promise as a solution for multidrug-resistant infections and should be further explored.

Challenges in Commercializing Peptide-Based Antimicrobial Agents

Production and Manufacturing Challenges

One of the main challenges in commercializing peptide-based antimicrobial agents lies in their production and manufacturing processes. Peptides are typically synthesized through solid-phase peptide synthesis (SPPS), which can be time-consuming and costly for large-scale production. The purification of peptides also presents difficulties due to their similarity in physicochemical properties, making it challenging to separate them from impurities effectively. Furthermore, ensuring batch-to-batch consistency and quality control during manufacturing is crucial but can be complex for peptide-based agents. Addressing these production and manufacturing challenges is essential to enable cost-effective and scalable commercialization of peptide-based antimicrobial agents.

Regulatory Hurdles

Navigating regulatory hurdles is another significant challenge when it comes to commercializing peptide-based antimicrobial agents. Regulatory agencies have stringent requirements for safety, efficacy, and quality assurance before approving new drugs for market distribution. Peptide-based agents may face additional scrutiny due to their unique nature compared to traditional small molecule drugs. Demonstrating the safety profile, pharmacokinetics, and clinical efficacy of these agents through rigorous preclinical and clinical trials is necessary but can be resource-intensive and time-consuming. Collaborations between researchers, pharmaceutical companies, and regulatory authorities are crucial to streamline the regulatory process and ensure the successful commercialization of peptide-based antimicrobial agents.

Market Acceptance and Pricing

Achieving market acceptance and establishing a viable pricing strategy are important considerations in the commercialization of peptide-based antimicrobial agents. The healthcare industry is highly competitive, and introducing new therapies requires demonstrating their value proposition compared to existing treatment options. Convincing healthcare providers, payers, and patients about the benefits of peptide-based agents for treating infections can be challenging, especially when considering factors such as cost-effectiveness, ease of administration, and patient compliance. Developing comprehensive marketing strategies that highlight the unique advantages of peptide-based agents while addressing concerns related to cost and accessibility is crucial for their successful adoption in the market.

Collaboration and Investment

Successful commercialization of peptide-based antimicrobial agents often requires collaboration between academia, pharmaceutical companies, and investors. Academic researchers play a vital role in advancing scientific knowledge and discovering novel peptides with therapeutic potential. Collaborations with pharmaceutical companies are necessary to further develop these peptides into viable drug candidates through preclinical testing, formulation optimization, and clinical trials. Additionally, securing investment from venture capitalists or government funding agencies is crucial to support research efforts, manufacturing scale-up, regulatory compliance, and marketing activities. Establishing strong partnerships between these stakeholders is essential for overcoming the challenges associated with commercializing peptide-based antimicrobial agents.

Peptide-based anti-antimicrobial agents offer a promising solution to combat the growing threat of antibiotic resistance. Through their unique mechanism of action, these agents have demonstrated potent antimicrobial activity against a wide range of pathogens. Moreover, their ability to selectively target bacteria while sparing host cells makes them an attractive alternative to traditional antibiotics. With further research and development, peptide-based anti-antimicrobial agents hold great potential for revolutionizing the field of infectious disease treatment.

Your Questions, Our Answers April 2024

What is the difference between antibiotics and antimicrobial peptides?

The majority of AMPs work by directly targeting and affecting bacterial cell membranes, resulting in an antibacterial effect. In contrast, antibiotics primarily kill bacteria by disrupting crucial metabolic processes, such as interfering with bacterial protein synthesis and inhibiting the replication of nucleic acids.

What are natural sources of antimicrobial peptides?

Antimicrobial peptides produced by mammals are released in the mucosal epithelial cells and paneth cells. Mammalian leukocytes are a valuable source of antimicrobial peptides, which play a crucial role in preventing bacterial infections.

What is an antimicrobial peptide?

Antimicrobial peptides (AMPs) are small peptides that are found in nature and play a vital role in the innate immune system of various organisms. They have a diverse range of actions, including inhibiting the growth of bacteria, fungi, parasites, and viruses.

What are the problems with antimicrobial peptides?

Nevertheless, AMPs can possess undesirable characteristics as medications, such as instability and toxicity. As a result, the development and creation of efficient AMPs necessitate comprehension of the mechanisms of established peptides and their impact on the human body.

What are examples of antimicrobial peptides?

Antimicrobial peptides can be derived from microorganisms such as bacteria and fungi. Popular examples of these peptides include nisin, gramicidin from Lactococcus lactis, Bacillus subtilis, and Bacillus brevis (Cao et al., 2018).

Which of the following is peptide antibiotic?

Polypeptide antibiotics include Bacitracin, Colistin, and Polymyxin B.

Peptide Discovery: Your Guide to Research and Application 2024

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Cite this Article

Cite this article as: Research Peptides Scientist, "Unlocking the Power of Peptide-Based Anti-Antimicrobial Agents: A Game-Changer in Fighting Bacterial Infections," in ResearchPeptides.net, November 6, 2023, https://researchpeptides.net/peptide-anti-antimicrobial-agents/. Accessed April 11, 2024.

 

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