Activity Of Antimicrobial Peptides Research Articles

Improving the Stability and Anti-Infective Activity of Sea Turtle AMPs Using Multiple Structural Modification Strategies.

Antimicrobial peptides (AMPs) are regarded as promising candidates for combating antimicrobial resistance. Previously we identified an AMP named Cm-CATH2 from the green sea turtle, which exhibited potent antibacterial activity and attractive potential in application. However, natural AMPs including Cm-CATH2 frequently suffer from structural instability and sensitivity to physiological conditions, limiting their effectiveness. Herein, we explored various strategies to enhance the efficacy and stability of Cm-CATH2, including peptide truncation, non-natural amino acid substitutions, disulfide bond-based cyclization, and stapled peptide techniques. The results demonstrated that the truncated NCM4 significantly improved the antimicrobial capability of Cm-CATH2 while also enhancing its anti-inflammatory and antibiofilm activities with minimal cytotoxicity. Further ornithine-substituted peptide oNCM markedly enhanced the stability of NCM4 without compromising its antimicrobial efficacy. This study successfully designed a lead peptide oNCM with significant development potential, while providing valuable insights into the advantages and limitations associated with diverse strategies for enhancing the stability of AMPs.

Novel active Trp- and Arg-rich antimicrobial peptides with high solubility and low red blood cell toxicity designed using machine learning tools.

Given the rising number of multidrug-resistant (MDR) bacteria, there is a need to design synthetic antimicrobial peptides (AMPs) that are highly active, non-hemolytic, and highly soluble to act as alternatives to antibiotics that are either no longer effective or used as drugs of last resort. Machine learning tools allow the straightforward in silico identification of non-hemolytic antimicrobial peptides. Here, we utilized a number of these tools to rank the best peptides from two libraries: 1) 8192 peptides with sequence bhxxbhbGAL, where b is the basic amino acid R or K, h is a hydrophobic amino acid, i.e. G, A, L, F, I, V, Y, or W and x is Q, S, A, or V; and 2) 512 peptides with sequence RWhxbhRGWL, where b and h are as for the first library and x is Q, S, A, or G. The top 100 sequences from each library, as well as 10 peptides predicted to be active but hemolytic (for a total of 220 peptides), were SPOT synthesized and their IC50 values were determined against S. aureus USA 300 (MRSA). Of these, 6 AMPs with low IC50's were characterized further in terms of: MICs against MRSA, E. faecalis, K. pneumoniae, E.coli and P. aeruginosa; RBC lysis; secondary structure in mammalian and bacterial model membranes; and activity against cancer cell lines HepG2, CHO, and PC-3. Overall, the approach yielded a large family of active antimicrobial peptides with high solubility and low red blood cell toxicity. It also provides a framework for future designs and improved machine learning tools.

Influence of hydrophobicity on the antimicrobial activity of helical antimicrobial peptides: a study focusing on three mastoparans.

Hydrophobicity is crucial for the interaction between amphipathic antimicrobial peptides and microbial pathogens. However, it is difficult to fully understand the impact of this factor because the biological functions are also influenced by other structural properties, including peptide length, net charge, hydrophilicity, secondary structure, and hydrophobic moment. This study compares three natural antimicrobial peptides-mastoparan C, mastoparan-AF, and mastoparan L-where hydrophobicity varies but other structural features remain nearly identical. Mastoparan C, the most hydrophobic peptide, displays the highest helical content and hemolytic activity, whereas mastoparan-AF, with slightly lower hydrophobicity, demonstrates superior selectivity. In contrast, mastoparan L, the least hydrophobic peptide, exhibits the weakest antimicrobial potency and lowest hemolytic activity, despite showing the least self-assembly. Overall, this study suggests that optimal hydrophobicity, rather than the highest value, enhances antimicrobial efficacy while minimizing hemolytic activity.

Evaluation of Novel HLM Peptide Activity and Toxicity against Planktonic and Biofilm Bacteria: Comparison to Standard Antibiotics.

Antibiotic resistance is one of the main concerns of public health, and the whole world is trying to overcome such a challenge by finding novel therapeutic modalities and approaches. This study has applied the sequence hybridization approach to the original sequence of two cathelicidin natural parent peptides (BMAP-28 and LL-37) to design a novel HLM peptide with broad antimicrobial activity. The physicochemical characteristics of the newly designed peptide were determined. As well, the new peptide's antimicrobial activity (Minimum Inhibitory Concentration (MIC), Minimum Bacterial Eradication Concentration (MBEC), and antibiofilm activity) was tested on two control (Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922) and two resistant (Methicillin-resistant Staphylococcus aureus (MRSA) ATCC BAA41, New Delhi metallo-beta- lactamase-1 Escherichia coli ATCC BAA-2452) bacterial strains. Furthermore, synergistic studies have been applied to HLM-hybridized peptides with five conventional antibiotics by checkerboard assays. Also, the toxicity of HLM-hybridized peptide was studied on Vero cell lines to obtain the IC50 value. Besides the percentage of hemolysis action, the peptide was tested in freshly heparinized blood. The MIC values for the HLM peptide were obtained as 20, 10, 20, and 20 μM, respectively. Also, the results showed no hemolysis action, with low to slightly moderate toxicity action against mammalian cells, with an IC50 value of 10.06. The Biomatik corporate labs, where HLM was manufactured, determined the stability results of the product by Mass Spectrophotometry (MS) and High-performance Liquid Chromatography (HPLC) methods. The HLM-hybridized peptide exhibited a range of synergistic to additive antimicrobial activities upon combination with five commercially available different antibiotics. It has demonstrated the biofilm-killing effects in the same concentration required to eradicate the control strains. The results indicated that HLM-hybridized peptide displayed a broad-spectrum activity toward different bacterial strains in planktonic and biofilm forms. It showed synergistic or additive antimicrobial activity upon combining with commercially available different antibiotics.

Aggregation-Prone Antimicrobial Peptides Target Gram-negative Bacterial Nucleic Acids and Protein Synthesis

Aggregation of antimicrobial peptides (AMPs) enhances their efficacy by destabilising the bacterial cell wall, membrane, and cytosolic proteins. Developing aggregation-prone AMPs offers a promising strategy to combat antibiotic resistance, though predicting such AMPs and understanding bacterial responses remain challenging. Octopus bimaculoides, a cephalopod species, lacks known AMP gene families, yet its protein fragments were used to predict AMPs via artificial intelligence tools. Four peptides (Oct-P1, Oct-P2, Oct-P3, and Oct-P4) were identified based on their aggregation propensity. Among them, Oct-P2 reduced the viability of Escherichia coli and Staphylococcus aureus by up to 90%, confirmed by confocal laser scanning microscopy and scanning electron microscopy. It further aggregated plasmid DNA in vitro, and the presence of extracellular DNA reduced their antibacterial activity. With knockout mutants, it revealed that Oct-P2 was internalised into bacterial cells, possibly through membrane transport proteins, enhancing its antibacterial effect. Aggregation-induced emission assays and molecular dynamics simulations revealed that Oct-P2 aggregates with transcription promoter DNA, inhibiting transcription and translation in vitro. This dual-target mechanism not only highlights the potential of Oct-P2 as a lead template for new antimicrobial drug development, but also opens a new window for discovering AMPs from protein fragments against the upcoming challenge of bacterial infections. Statement of significanceA popular strategy for identifying antimicrobial peptides (AMPs) in specific genomes uses the conserved regions of AMP families, but this strategy has limitations in organisms lacking classical AMP gene families, such as Octopus. Fragments from non-antimicrobial proteins serve as a rich source for the identification of new AMPs. In this study, we used artificial intelligence tools to search for potential candidate AMP sequences from non-antimicrobial proteins in Octopus bimaculoides. The successful identification of aggregation-prone AMPs was shown to decrease bacterial viability, increase permeability, and reduce biomass. One candidate, Oct-P2, kills the gram-negative bacteria E. coli by aggregating with DNA and inhibiting transcription and translation, suggesting a new intracellular mechanism of AMP activity.

Advances in Artificially Designed Antibacterial Active Antimicrobial Peptides.

Antibacterial resistance has emerged as a significant global concern, necessitating the urgent development of new antibacterial drugs. Antimicrobial peptides (AMPs) are naturally occurring peptides found in various organisms. Coupled with a wide range of antibacterial activity, AMPs are less likely to develop drug resistance and can act as potential agents for treating bacterial infections. However, their characteristics, such as low activity, instability, and toxicity, hinder their clinical application. Consequently, researchers are inclined towards artificial design and optimization based on natural AMPs. This review discusses the research advancements in the field of artificial designing and optimization of various AMPs. Moreover, it highlights various strategies for designing such peptides, aiming to provide valuable insights for developing novel AMPs.

Insights into an indolicidin-derived low-toxic anti-microbial peptide's efficacy against bacterial cells while preserving eukaryotic cell viability.

Antimicrobial peptides (AMPs) are a current solution to combat antibiotic resistance, but they have limitations, including their expensive production process and the induction of cytotoxic effects. We have developed novel AMP candidate (peptide 3.1) based on indolicidin, among the shortest naturally occurring AMP. The antimicrobial activity of this peptide is demonstrated by the minimum inhibitory concentration, while the hemolysis tests and MTT assay indicate its low cytotoxicity. In optical diffraction tomography, red blood cells treated with peptide 3.1 showed no discernible effects, in contrast to indolicidin. However, peptide 3.1 did induce cell lysis in E. coli, leading to a reduced potential for the development of antibiotic resistance. To investigate the mechanism underlying membrane selectivity, the structure of peptide 3.1 was analyzed using nuclear magnetic resonance spectroscopy and molecular dynamics simulations. Peptide 3.1 is structured with an increased distinction between hydrophobic and charged residues and remained in close proximity to the eukaryotic membrane. On the other hand, peptide 3.1 exhibited a disordered conformation when approaching the prokaryotic membrane, similar to indolicidin, leading to its penetration into the membrane. Consequently, it appears that the amphipathicity and structural rigidity of peptide 3.1 contribute to its membrane selectivity. In conclusion, this study may lead to the development of Peptide 3.1, a promising commercial candidate based on its low cost to produce and low cytotoxicity. We have also shed light on the mechanism of action of AMP, which exhibits selective toxicity to bacteria while not damaging eukaryotic cells.

Antimicrobial Peptides: The Game-Changer in the Epic Battle Against Multidrug-Resistant Bacteria.

The rapid progress of antibiotic resistance among bacteria has prompted serious medical concerns regarding how to manage multidrug-resistant (MDR) bacterial infections. One emerging strategy to combat antibiotic resistance is the use of antimicrobial peptides (AMPs), which are amino acid chains that act as broad-spectrum antimicrobial molecules and are essential parts of the innate immune system in mammals, fungi, and plants. AMPs have unique antibacterial mechanisms that offer benefits over conventional antibiotics in combating drug-resistant bacterial infections. Currently, scientists have conducted multiple studies on AMPs for combating drug-resistant bacterial infections and found that AMPs are a promising alternative to conventional antibiotics. On the other hand, bacteria can develop several tactics to resist and bypass the effect of AMPs. Therefore, it is like a battle between the bacterial community and the AMPs, but who will win? This review provides thorough insights into the development of antibiotic resistance as well as detailed information about AMPs in terms of their history and classification. Furthermore, it addresses the unique antibacterial mechanisms of action of AMPs, how bacteria resist these mechanisms, and how to ensure AMPs win this battle. Finally, it provides updated information about FDA-approved AMPs and those that were still in clinical trials. This review provides vital information for researchers for the development and therapeutic application of novel AMPs for drug-resistant bacterial infections.

Myxinidin-analogs able to sequester Fe(III): Metal-based gun to combat Pseudomonas aeruginosa biofilm

Bacteria have developed a tendency to form biofilms, where bacteria live in organized structures embedded in a self-produced matrix of DNA, proteins, and polysaccharides. Additionally, bacteria need iron(III) as an essential nutrient for bacterial growth and secrete siderophore groups that sequester it from the environment. To design a molecule able both to inhibit the bacteria and to sequester iron, we developed two hydroxamate-based peptides derived from an analog (WMR-4), previously developed in our lab, of the antimicrobial peptide myxinidin.In detail, we proposed a combination of WMR-4 with the hydroxamic acid resulting in the peptides WMR-7 and WMR-16 which differ for the length of the linker between the antimicrobial moiety and the siderophore. Both peptides were characterized through a set of different biophysical experiments to investigate their ability to sequester Fe3+. The peptide‑iron(III) complexes were studied through the UV–visible spectroscopy in organic solvent to eliminate water competition, and in acidic water to avoid iron precipitation. The complexes were also characterized by performing electrochemistry, circular dichroism and NMR spectroscopy experiments. In addition, we demonstrated the ability of peptide‑iron(III) complexes to inhibit the biofilm of Pseudomonas aeruginosa and to have an impact on the cell motility. This metal-based approach consisting in a hydroxamic acid conjugation represents a promising strategy to enhance the antibiofilm activity of antimicrobial peptides against one of most dangerous bacteria such as Pseudomonas aeruginosa.

DbAMP 3.0: updated resource of antimicrobial activity and structural annotation of peptides in the post-pandemic era.

Antimicrobial resistance is one of the most urgent global health threats, especially in the post-pandemic era. Antimicrobial peptides (AMPs) offer a promising alternative to traditional antibiotics, driving growing interest in recent years. dbAMP is a comprehensive database offering extensive annotations on AMPs, including sequence information, functional activity data, physicochemical properties and structural annotations. In this update, dbAMP has curated data from over 5200 publications, encompassing 33,065 AMPs and 2453 antimicrobial proteins from 3534 organisms. Additionally, dbAMP utilizes ESMFold to determine the three-dimensional structures of AMPs, providing over 30,000 structural annotations that facilitate structure-based functional insights for clinical drug development. Furthermore, dbAMP employs molecular docking techniques, providing over 100 docked complexes that contribute useful insights into the potential mechanisms of AMPs. The toxicity and stability of AMPs are critical factors in assessing their potential as clinical drugs. The updated dbAMP introduced an efficient tool for evaluating the hemolytic toxicity and half-life of AMPs, alongside an AMP optimization platform for designing AMPs with high antimicrobial activity, reduced toxicity and increased stability. The updated dbAMP is freely accessible at https://awi.cuhk.edu.cn/dbAMP/. Overall, dbAMP represents a comprehensive and essential resource for AMP analysis and design, poised to advance antimicrobial strategies in the post-pandemic era.

Stereorandomized Oncocins with Preserved Ribosome Binding and Antibacterial Activity.

We recently showed that solid-phase peptide synthesis using racemic amino acids yields stereorandomized peptides comprising all possible diastereomers as homogeneous, single-mass products that can be purified by HPLC and that stereorandomization modulates activity, toxicity, and stability of membrane-disruptive cyclic and linear antimicrobial peptides (AMPs) and dendrimers. Here, we tested if stereorandomization might be compatible with target binding peptides with the example of the proline-rich AMP oncocin, which inhibits the bacterial ribosome. Stereorandomization of up to nine C-terminal residues preserved ribosome binding and antibacterial effects including activities against drug-resistant bacteria and protected against serum degradation. Surprisingly, fully stereorandomized oncocin was as active as L-oncocin in dilute growth media stimulating peptide uptake, although it did not bind the ribosome, indicative of an alternative mechanism of action. These experiments show that stereorandomization can be compatible with target binding peptides and can help understand their mechanism of action.

Development of α-Helical Antimicrobial Peptides with Imperfect Amphipathicity for Superior Activity and Selectivity.

The advancement of antimicrobial peptides (AMPs) as therapeutic agents is hindered by their poor selectivity. Recent evidence indicates that controlled disruption of the amphipathicity of α-helical AMPs may increase the selectivity. This study investigated the role of imperfect amphipathicity in optimizing AMPs with varied sequences to enhance their activity and selectivity. Among these, the lead peptide RI-18, characterized by an imperfectly amphipathic α-helical structure, demonstrated potent and broad-spectrum antibacterial activity without inducing hemolytic or cytotoxic effects. RI-18 effectively eliminated planktonic and biofilm-associated bacteria as well as persister cells and exhibited high bacterial plasma membrane affinity, inducing rapid membrane permeabilization and rupture. Notably, RI-18 significantly reduced bacterial loads without promoting bacterial resistance, highlighting its therapeutic potential. Overall, this study identified RI-18 as a promising antimicrobial candidate. The rational strategy of tuning imperfect amphipathicity to enhance the AMP activity and selectivity may facilitate the design and development of AMPs.

Recent Discoveries of Antifungal Activity in Plant Antimicrobial Peptides

Recent Discoveries of Antifungal Activity in Plant Antimicrobial Peptides

LiaR-dependent gene expression contributes to antimicrobial responses in group A Streptococcus.

The ability to sense and respond to host defenses is essential for pathogen survival. Some mechanisms involve two-component systems (TCSs) that respond to host molecules, such as antimicrobial peptides (AMPs), and activate specific gene regulatory pathways to aid in survival. Alongside TCSs, bacteria coordinate cell division proteins, chaperones, cell wall sortases, and secretory translocons at discrete locations within the cytoplasmic membrane, referred to as functional membrane microdomains (FMMs). In group A Streptococcus (GAS), the FMM or "ExPortal" coordinates protein secretion, cell wall synthesis, and sensing of AMP-mediated cell envelope stress via the LiaFSR three-component system. Previously, we showed that GAS exposure to a subset of AMPs (α-defensins) activates the LiaFSR system by disrupting LiaF and LiaS co-localization in the ExPortal, leading to increased LiaR phosphorylation, expression of the transcriptional regulator SpxA2, and altered GAS virulence gene expression. The mechanisms by which LiaFSR integrates cell envelope stress with responses to AMP activity and virulence are not fully elucidated. Here, we show the LiaFSR regulon is comprised of genes encoding SpxA2 and three membrane-associated proteins: a PspC domain-containing protein (PCP), the lipoteichoic acid-modifying protein LafB, and the membrane protein insertase YidC2. Our data support that phosphorylated LiaR induces transcription of these genes via a conserved operator, whose disruption attenuates GAS virulence and increases susceptibility to AMPs in a manner primarily dependent on differential expression of SpxA2. Our work expands our understanding of the LiaFSR regulatory network in GAS and identifies targets for further investigation of mechanisms of cell envelope stress tolerance contributing to GAS pathogenesis.

Investigation of the Mechanism of Action of AMPs from Amphibians to Identify Bacterial Protein Targets for Therapeutic Applications.

Antimicrobial peptides (AMPs) from amphibians represent a promising source of novel antibacterial agents due to their potent and broad-spectrum antimicrobial activity, which positions them as valid alternatives to conventional antibiotics. This review provides a comprehensive analysis of the mechanisms through which amphibian-derived AMPs exert their effects against bacterial pathogens. We focus on the identification of bacterial protein targets implicated in the action of these peptides and on biological processes altered by the effect of AMPs. By examining recent advances in countering multidrug-resistant bacteria through multi-omics approaches, we elucidate how AMPs interact with bacterial membranes, enter bacterial cells, and target a specific protein. We discuss the implications of these interactions in developing targeted therapies and overcoming antibiotic resistance (ABR). This review aims to integrate the current knowledge on AMPs' mechanisms, identify gaps in our understanding, and propose future directions for research to harness amphibian AMPs in clinical applications.

Antimicrobial Peptides: Mechanism, Expressions, and Optimization Strategies.

Antimicrobial peptides (AMPs) are favoured because of their broad-spectrum antimicrobial properties and because they do not easily develop microbial resistance. However, the low yield and difficult extraction processes of AMPs have become bottlenecks in large-scale industrial applications and scientific research. Microbial recombinant production may be the most economical and effective method of obtaining AMPs in large quantities. In this paper, we review the mechanism, summarize the current status of microbial recombinant production, and focus on strategies to improve the yield and activity of AMPs, in order to provide a reference for their large-scale production.

Characterization of Structural Properties and Antimicrobial Activity of the C3f Peptide of Complement System.

The C3f peptide is a by-product of regulation of the activated complement system with no firmly established function of its own. We have previously shown that C3f exhibits moderate antimicrobial activity against some Gram-positive bacteria invitro. Presence of two histidine residues in the amino acid sequence of the peptide suggests enhancement of its antimicrobial activity at lower pH and in the presence of metal cations, particularly zinc cations. Since such conditions could be realized in inflammatory foci, the study of dependence of C3f activity on pH and presence of metal cations could provide an opportunity to assess biological significance of antimicrobial properties of the peptide. The peptide C3f and its analogs with histidine residues substituted by lysines or serines, C3f[H/K] and C3f[H/S], were prepared by solid-phase synthesis. Using CD spectroscopy, we found that C3f contained a β-hairpin and unstructured regions; presence of Zn2+ did not affect conformation of the peptide. In the present work, it was shown that C3f could also exhibit antimicrobial activity against Gram-negative bacteria, in particular, Pseudomonas aeruginosa ATCC 27583. Exposure of P.aeruginosa and Listeria monocytogenes EGD to the peptide was accompanied by disruption of the barrier function of bacterial membranes. Zn2+ ions, unlike Cu2+ ions, enhanced antimicrobial activity of C3f against L.monocytogenes, with 4- and 8-fold molar excess of Zn2+ being no more effective than a 20% excess. Activity of the C3f analogs was also enhanced to some extent by the zinc ions. Thus, we hypothesize existence of the histidine-independent formation of C3f-Zn2+ complexes leading to increase in the total charge and antimicrobial activity of the peptide. In the presence of 0.15M NaCl, C3f lost its antimicrobial activity regardless of the presence of Zn2+, indicating an insignificant role of C3f as an endogenous antimicrobial peptide. Presence of C3f eliminated bactericidal effect of Zn2+ against the zinc-sensitive Escherichia coli strain ESBL 521/17, indirectly confirming interaction of the peptide with Zn2+. Activity of C3f against Micrococcus luteus A270 increased with decreasing pH, while effect of pH on the C3f activity against L.monocytogenesis was more complex. In this work, we show significance of the factors such as pH and metal cations in realization of antimicrobial activity of peptides based on the example of C3f.

Novel Tree Shrew-Derived Antimicrobial Peptide with Broad-Spectrum Antibacterial Activity.

The number of cationic residues and net charge are critical for the activity of antimicrobial peptides (AMPs) due to their role in facilitating initial electrostatic interactions with negatively charged bacterial membranes. A cathelicidin AMP (TC-33) has been identified from the Chinese tree shrew in our previous work, which exhibited weak antimicrobial activity, likely due to its moderately cationic nature. In the current study, based on TC-33, we designed a novel AMP by peptide truncation and Glu substitutions to increase its net cationic charge from +4 to +8. The resulting peptide, TC-LAR-18, showed 4-128-fold enhanced antimicrobial activity relative to TC-33 without causing hemolysis and cytotoxicity within 100 μg/mL. TC-LAR-18 effectively eliminated both planktonic and biofilm-associated bacteria, demonstrating rapid bactericidal effects due to its ability to quickly penetrate and disrupt bacterial cell membranes with a low propensity to induce resistance. Notably, TC-LAR-18 provided substantial protection against skin bacterial infection in mice, underscoring its therapeutic potential. These findings not only highlight the importance of positively charged residues for the antibacterial activity of AMPs but also present a useful drug candidate for combating multidrug-resistant bacteria.

Effective combinations of silver nanoparticles and antimicrobial peptides against antibiotic-resistant bacteria

BACKGROUND: The problem of constantly growing resistance of microorganisms to the antibiotics used forces scientists to constantly search for new antimicrobial agents. AIM: To study the antimicrobial activity and toxicity of silver nanoparticles and antimicrobial peptides with a β-hairpin structure, and to characterize their combined antimicrobial action. MATERIALS AND METHODS: The antimicrobial activity of silver nanoparticles and antimicrobial peptides against antibiotic-resistant bacteria was assessed by serial dilutions in a liquid nutrient medium, and the combined antimicrobial activity – by serial dilutions according to the “checkerboard” method. The toxicity of the substances to human cells was determined using a hemolytic test. RESULTS: The studied silver nanoparticles have pronounced antimicrobial activity and low toxicity to human erythrocytes. Silver nanoparticles containing acetylcysteine are more active against gram-negative bacteria than against gram-positive ones. Synergism of the antibacterial action was detected with the combined use of silver nanoparticles stabilized with sodium oleate and protegrin-1. A synergistic antimicrobial effect was also noted for combinations of silver nanoparticles containing acetylcysteine with protegrin-1, ricaecilin and shuchin-4. CONCLUSIONS: Effective combinations of silver nanoparticles and antimicrobial peptides have been identified that act synergistically against antibiotic-resistant bacterial strains, i.e. they multiply the effect of each other. These combinations can be used as prototypes for the development of antibacterial drugs.

Activity of protegrin-1 against mouse Ehrlich ascites carcinoma <i>in vitro</i> and <i>in vivo</i>

BACKGROUND: The problem of multidrug resistance in cancer treatment creates an urgent demand for developing new effective antitumor agents. Due to the unusual mechanism of recognizing and damaging tumor cells, antimicrobial peptides are considered as possible prototypes for designing such therapeutics. AIM: This work was aimed to compare the antitumor potential of the promising membranolytic antimicrobial peptide protegrin-1 in vitro and in vivo in Ehrlich ascites carcinoma mice model. MATERIALS AND METHODS: We used two variants of the model by inducing a tumor in solid or ascites form. In the first case, the mice were injected with the peptide twice a week for three weeks, and in the second injections were provided every other day for six days. The activity of antimicrobial peptides against isolated Ehrlich ascites carcinoma cells in vitro was analyzed using MTT-test. RESULTS: Protegrin-1 demonstrated high activity against Ehrlich ascites carcinoma cells in vitro, but had no significant effect on the lifespan of mice bearing solid or ascites form of Ehrlich tumor at the dosing and administration regimens we used. However, treatment with protegrin-1 caused a decrease in the ascites volume and in the number of cells in the ascites fluid. CONCLUSIONS: Protegrin-1 retains its antitumor properties in vivo, but it may be presumed, that to effectively suppress tumor growth it requires a more frequent and prolonged administration compared with conventional antitumor antibiotics, of which we adopted the administration regimen for protegrin-1 in this study.