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Antimicrobial peptides (AMPs) have received considerable attention as next-generation drugs for infectious diseases. Amphipathicity and the formation of a stabilized secondary structure are required to exert their antimicrobial activity by insertion into the microbial membrane, resulting in lysis of the bacteria. We previously reported the development of a novel antimicrobial peptide, 17KKV, based on the Magainin 2 sequence. The peptide was obtained by increasing the amphipathicity due to the replacement of amino acid residues. Moreover, we studied the structural development of 17KKV and revealed that the secondary structural control of 17KKV by the introduction of non-proteinogenic amino acids such as α,α-disubstituted amino acids or side-chain stapling enhanced its antimicrobial activity. Among them, peptide 1, which contains 2-aminobutyric acid residues in the 17KKV sequence, showed potent antimicrobial activity against multidrug-resistant Pseudomonus aeruginosa (MDRP) without significant hemolytic activity against human red blood cells. However, the effects of cationic amino acid substitutions on secondary structures and antimicrobial activity remain unclear. In this study, we designed and synthesized a series of peptide 1 by the replacement of Lys residues with several types of cationic amino acids and evaluated their secondary structures, antimicrobial activity, hemolytic activity, and resistance against digestive enzymes.

In vitro determination of hemolytic properties is a common and important method for preliminary evaluation of cytotoxicity of chemicals, drugs, or any blood-contacting medical device or material. The method itself is relatively straightforward, however, protocols used in the literature vary substantially. This leads to significant difficulties both in interpreting and in comparing the obtained values. Here, we examine how the different variables used under different experimental setups may affect the outcome of this assay. We find that certain key parameters affect the hemolysis measurements in a critical manner. The hemolytic effect of compounds tested here varied up to fourfold depending on the species of the blood source. The use of different types of detergents used for generating positive control samples (i.e., 100% hemolysis) produced up to 2.7-fold differences in the calculated hemolysis ratios. Furthermore, we find an expected, but substantial, increase in the number of hemolyzed erythrocytes with increasing erythrocyte concentration and with prolonged incubation time, which in turn affects the calculated hemolysis ratios. Based on our findings we propose an optimized protocol in an attempt to standardize future hemolysis studies.

Antimicrobial peptides (AMPs) are essential elements of thehost defense system. Characterized by heterogenous structures and broad‐spectrumaction, they are promising candidates for combating multidrug resistance. Thecombined use of AMPs with other antimicrobial agents provides a new arsenal ofdrugs with synergistic action, thereby overcoming the drawback of monotherapiesduring infections. AMPs kill microbes via pore formation, thus inhibitingintracellular functions. This mechanism of action by AMPs is an advantage overantibiotics as it hinders the development of drug resistance. The synergisticeffect of AMPs will allow the repurposing of conventional antimicrobials andenhance their clinical outcomes, reduce toxicity, and, most significantly,prevent the development of resistance. In this review, various synergies ofAMPs with antimicrobials and miscellaneous agents are discussed. The effect ofstructural diversity and chemical modification on AMP properties is firstaddressed and then different combinations that can lead to synergistic action,whether this combination is between AMPs and antimicrobials, or AMPs andmiscellaneous compounds, are attended. This review can serve as guidance whenredesigning and repurposing the use of AMPs in combination with other antimicrobialagents for enhanced clinical outcomes.

The rapid rise of multidrug-resistant (MDR) bacteria has once again caused bacterial infections to become a global health concern. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), offer a viable solution to these pathogens due to their diverse mechanisms of actions, which include direct killing as well as immunomodulatory properties (e.g., anti-inflammatory activity). HDPs may hence provide a more robust treatment of bacterial infections. In this review, the advent of and the mechanisms that lead to antibiotic resistance will be described. HDP mechanisms of antibacterial and immunomodulatory action will be presented, with specific examples of how the HDP aurein 2.2 and a few of its derivatives, namely peptide 73 and cG4L73, function. Finally, resistance that may arise from a broader use of HDPs in a clinical setting and methods to improve biocompatibility will be briefly discussed.

Antimicrobial peptides (AMPs) possess great potential for combating drug-resistant bacteria. Thanatin is a pathogen-inducible single-disulfide-bond-containing β-hairpin AMP which was first isolated from the insect Podisus maculiventris. The 21-residue-long thanatin displays broad-spectrum activity against both Gram-negative and Gram-positive bacteria as well as against various species of fungi. Remarkably, thanatin was found to be highly potent in inhibiting the growth of bacteria and fungi at considerably low concentrations. Although thanatin was isolated around 25 years ago, only recently has there been a pronounced interest in understanding its mode of action and activity against drug-resistant bacteria. In this review, multiple modes of action of thanatin in killing bacteria and in vivo activity, therapeutic potential are discussed. This promising AMP requires further research for the development of novel molecules for the treatment of infections caused by drug resistant pathogens.

Amphibian skin is a mucosal surface in direct and continuous contact with a microbially diverse and laden aquatic and/or terrestrial environment. As such, frog skin is an important innate immune organ and first line of defence against pathogens in the environment. Critical to the innate immune functions of frog skin are the maintenance of physical, chemical, cellular, and microbiological barriers and the complex network of interactions that occur across all the barriers. Despite the global decline in amphibian populations, largely as a result of emerging infectious diseases, we understand little regarding the cellular and molecular mechanisms that underlie the innate immune function of amphibian skin and defence against pathogens. In this review, we discuss the structure, cell composition and cellular junctions that contribute to the skin physical barrier, the antimicrobial peptide arsenal that, in part, comprises the chemical barrier, the pattern recognition receptors involved in recognizing pathogens and initiating innate immune responses in the skin, and the contribution of commensal microbes on the skin to pathogen defence. We briefly discuss the influence of environmental abiotic factors (natural and anthropogenic) and pathogens on the immunocompetency of frog skin defences. Although some aspects of frog innate immunity, such as antimicrobial peptides are well-studied; other components and how they contribute to the skin innate immune barrier, are lacking. Elucidating the complex network of interactions occurring at the interface of the frog's external and internal environments will yield insight into the crucial role amphibian skin plays in host defence and the environmental factors leading to compromised barrier integrity, disease, and host mortality.

Microbial biofilms are becoming increasingly difficult to treat in the medical setting due to their intrinsic resistance to antibiotics. To combat this, several biofilm dispersal agents are currently being developed as treatments for biofilm infections. Combining biofilm dispersal agents with antibiotics is emerging as a promising strategy to simultaneously disperse and eradicate biofilms or, in some cases, even inhibit biofilm formation. Here we review studies that have investigated the anti-biofilm activity of some well-studied biofilm dispersal agents (e.g., quorum sensing inhibitors, nitric oxide/nitroxides, antimicrobial peptides/amino acids) in combination with antibiotics from various classes. This review aims to directly compare the efficacy of different combination strategies against microbial biofilms and highlight synergistic treatments that warrant further investigation. By comparing across studies that use different measures of efficacy, we can conclude that treating biofilms in vitro and, in some limited cases in vivo , with a combination of an anti-biofilm agent and an antibiotic, appears overall more effective than treating with either compound alone. The review identifies the most promising combination therapies currently under development as biofilm inhibition and eradication therapies.

Antimicrobial peptides (AMPs) have broad-spectrum antimicrobial activity, enabling them to rapidly detect and eliminate targets. In addition, many AMPs are natural peptides, making them promising candidates for therapeutic drugs. This review discusses the basic properties and mechanisms of action of AMPs, highlighting their ability to disrupt microbial membranes and modulate host immune responses. It also reviews the current state of research into using AMPs against various viral infections, focusing on their therapeutic potential against viruses that contribute to the global health crisis. Despite promising developments, therapies based on AMPs still face challenges such as stability, toxicity, and production costs. In this text, we will discuss these challenges and the latest technological advances aimed at overcoming them. The combination of nanotechnology and bioengineering approaches offers new ways to enhance the delivery, efficacy, and safety of AMPs. We emphasize the importance of further research to fully exploit the potential of AMPs in antiviral therapy, advocating a multifaceted approach that includes optimizing clinical use and exploring synergies with existing antiviral drugs.

Bacterial infections occur when wound healing fails to reach the final stage of healing, which is usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site, which is accompanied very often by increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies that are used to combat infection and modulate the healing rate—such as polymers, scaffolds, films and wound dressings, and organic and inorganic nanoparticles—have been discussed as well. New technologies such as Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated protein (CRISPR-Cas) are taken into consideration as potential future tools for AMP delivery in skin therapy.

Changes in the structure and function of the microbiota are associated with various human diseases. These microbial changes can be mediated by antimicrobial peptides (AMPs), small peptides produced by the host and their microbiota, which play a crucial role in host-bacteria co-evolution. Thus, by studying AMPs produced by the microbiota (microbial AMPs), we can better understand the interactions between host and bacteria in microbiome homeostasis. Additionally, microbial AMPs are a new source of compounds against pathogenic and multi-resistant bacteria. Further, the growing accessibility to metagenomic and metatranscriptomic datasets presents an opportunity to discover new microbial AMPs. This review examines the structural properties of microbiota-derived AMPs, their molecular action mechanisms, genomic organization, and strategies for their identification in any microbiome data as well as experimental testing. Overall, we provided a comprehensive overview of this important topic from the microbial perspective.