AMPs act mainly by direct interactions with microbial cell membranes. In most cases, attack-specific biochemical targets, AMPs take advantage of the natural structural distinctions between microbial and host cell membranes [35]. The majority of AMPs are cationic and amphipathic and thus have the capacity to associate electrostatically with negatively charged microbial surface molecules, including lipopolysaccharides in Gram-negative bacteria and teichoic acids in Gram-positive bacteria. When bound, AMPs insert into the lipid bilayer, leading to physical disruption that creates leakage of cytoplasmic contents and cell death in minutes [36]. Multiple models have been proposed to explain this mechanism. The barrel stave model assumes that peptides stack perpendicularly to create transmembrane pores similar to barrel staves. The toroidal pore model infers that peptides create bilayer curvature, leading to pore lining by peptides and lipid head groups [37]. In the carpet model, peptides blanket the membrane surface as a carpet until a critical concentration is attained, resulting in micellization and membrane disruption [38]. These mechanisms are rapid, thus preventing the emergence of microbial resistance. In general, the membrane targeting strategy confers potent, broad-spectrum antimicrobial activity to AMPs, highlighting their value as alternatives to traditional antibiotics [39]. Unlike conventional antibiotics, which normally target specific biochemical pathways such as protein synthesis or cell wall formation, AMPs exert a multi-mechanistic mode of action that makes the development of resistance by pathogens. This is more effective against multi-drug resistant (MDR) strains, including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, and Pseudomonas aeruginosa. The Gram-negative bacteria are more effectively targeted by AMPs due to their outer membrane disruption ability, leading to the destabilization of the lipid bilayer; this is not common for a wide range of conventional antibiotics. The comparative studies further suggest that beyond an induction of more rapid bactericidal effects, AMPs exhibit immunomodulatory and anti-biofilm activity, which further distinguishes them from conventional antibiotics.

Besides direct disruption of microbial membranes, many AMPs employ non-membrane targeting modes of action for exerting their antimicrobial activity [55]. In contrast to membrane targeting AMPs, these AMPs can cross the lipid bilayer without inducing pronounced structural alterations, thus gaining access to intracellular targets. Once intracellularly localized, they can interfere with vital processes required for microbial survival and cell division. A typical mechanism of action involves the blockage of nucleic acid synthesis by peptides such as indolicidin or buforin II binding to DNA or RNA with the attendant prevention of transcription, replication, and other nucleic acid-dependent activities [56]. A further important target is protein synthesis; examples here include proline-enriched AMPs such as Bac7 that interact with ribosomal machinery, with translation being blocked and thus preventing cellular growth [57]. AMPs also inhibit cell wall biosynthesis as a mechanism; examples here include nisin, which binds lipid II, which is an important precursor during peptidoglycan assembly, such that eventually cell wall integrity can be compromised. Non-membrane targeting AMPs provide a multi-faceted approach towards microbial control by limiting the chances of resistance development as various intracellular pathways can be blocked concurrently [58]. The intracellular mechanism of action, coupled with selective targeting towards microbial cells, confers enhanced therapeutics on AMPs as next-generation antimicrobial molecules capable of combating multidrug-resistant pathogens.

Alpha-helical AMPs are a well-studied group of AMPs characterized by the ability to form an α-helical structure when interacting with the microbial membrane [69]. When dissolved, they tend to be unstructured or form a random coil structure. However, on interacting with the lipid bilayer of microbial cells, their amphipathic character enables them to fold into an α-helix, and hydrophobic residues are oriented towards the lipid interior of the membrane while hydrophilic or cationic residues face the aqueous phase [70]. This amphipathic α-helical structure is critical for the interaction with the membrane by enabling the peptide to insert into and destabilize the microbial membrane efficiently. The major mode of action of α-helical peptides is membrane targeting, but others have intracellular activity as well. After binding to the membrane, peptides like magainins (from frog skin) and human cathelicidin LL-37 are deposited on the surface of the membrane [71]. Dependent on the membrane composition and peptide concentration, they are able to disrupt the membrane through one of a number of models: barrel stave pore formation, in which peptides insert perpendicularly to form transmembrane pores; toroidal pores, in which peptides and lipid head groups line the pore; or the carpet model, in which peptides coat the surface of the membrane and cause disintegration in a detergent like process. This leads to leakage of cytoplasmic contents, loss of membrane potential, and quick microbial cell death. Magainins, purified from Xenopus laevis skin, operate through toroidal pore formation, demonstrating broad-spectrum activity against Gram-negative and Gram-positive bacteria, fungi, and certain protozoa. LL-37, a human cathelicidin, not only forms α-helices to disrupt membranes but also has immunomodulatory activity and acts for wound healing [72]. The structural flexibility and broad-spectrum nature of α-helical AMPs make them very promising therapeutic candidates, especially against multidrug-resistant organisms (Figure 2).

Beta-sheet AMPs are a structurally distinct class characterized by the presence of intramolecular disulfide bridges that stabilize their β-sheet structure. Unlike α-helical peptides, β-sheet AMPs have a preformed, rigid secondary structure even in solution, which accounts for their stability and resistance to proteolytic digestion [73]. The amphipathic character of β-sheet peptides allows for selective interaction with microbial membranes: positively charged residues interact with negatively charged elements of bacterial membranes, e.g., lipopolysaccharides in Gram-negative bacteria or teichoic acids in Gram-positive bacteria, and hydrophobic residues insert into the lipid bilayer. The major mode of action of β-sheet peptides is membrane targeting. After adhering to the microbial surface, these peptides may cause membrane permeabilization and pore formation, leading to the leakage of ions and vital cytoplasmic materials, ultimately causing cell death [74]. Certain β-sheet AMPs, including defensins, are also able to aggregate to create multimeric complexes that increase membrane disruption. Some β-sheet peptides are also immunomodulatory, inducing chemotaxis, cytokine release, and other host defence mechanisms. Defensins, in humans, mammals, and plants, are traditional β-sheet AMPs that are supported by three to four disulfide bridges [75]. Defensins have broad-spectrum antimicrobial action against bacteria, fungi, and certain viruses by causing membrane permeabilization. Their structural stability and multifunctionality make β-sheet peptides very potent as innate immune effectors and potential therapeutic agents, especially against multidrug-resistant pathogens (Figure 2) [76].

Long or disordered AMPs are a unique class of peptides that lack a stable secondary structure in solution. Unlike α-helical or β-sheet peptides, these molecules do not adopt a stable form until they engage with microbial membranes or intracellular targets. Their inherent flexibility facilitates them to conform to different environments and bind well to various molecular targets. Long peptides are often highly enriched in particular amino acids like proline, glycine, tryptophan, or arginine, which provide distinctive chemical characteristics [77]. Proline and glycine provide structural adaptability, and tryptophan provides favorable interactions with lipid membranes via aromatic stacking and hydrophobic forces. The mode of action of unstructured or extended peptides is intricate. Most of these peptides are non-membrane targeting in their activity through translocation through microbial membranes with minimal disruption and then interfering with essential intracellular processes. For example, indolicidin, a 13-residue peptide from bovine neutrophils, has the ability to penetrate bacterial membranes and interact directly with DNA and RNA to inhibit nucleic acid synthesis and transcription, and replication [78]. Besides intracellular delivery, some extended peptides also possess membrane-disruptive activity at higher doses, disrupting the lipid bilayer in a carpet fashion. The flexibility of extended peptides enables them to deliver a wide range of microorganisms, such as Gram-positive and Gram-negative bacteria, fungi, and viruses. They are small in size, rich in positively charged residues, and have flexible conformations, which increase cell penetration and binding specificity. This dual mechanism, entailing intracellular targeting coupled with possible membrane disruption, makes extended or unstructured AMPs extremely effective against multidrug-resistant pathogens [79]. Elucidation of their structure-function relationships is important in designing synthetic analogues with improved stability, potency, and therapeutic utility. Indolicidin is a case in point, which exhibits robust antibacterial, antifungal, and antiviral activities, as well as a model for the rational development of new peptide-based therapeutics (Figure 2) [80].

Cyclic AMPs are a unique class of peptides characterized by covalent cyclization, either through head-to-tail cyclization or through side chain linkages. This structural restriction imparts greater stability, proteolytic resistance, and enhanced bioavailability compared to linear peptides. The cyclic structure also allows the preservation of a structured amphipathic presentation, which is vital for selective interaction with microbial membranes and intracellular targets [81]. Most cyclic peptides are rich in hydrophobic and cationic residues, facilitating strong electrostatic attraction against negatively charged bacterial membranes with minimal toxicity against host cells. The mode of action of cyclic peptides is complex. They can lyse microbial membranes by pore formation or membrane disruption, similar to α-helical and β-sheet peptides. Additionally, some cyclic peptides, like lantibiotics, inhibit bacterial elements, such as lipid II, a vital precursor of peptidoglycan assembly, consequently slowing cell wall development [82]. Their stable conformation also allows them to penetrate microbial cells for intracellular target interference, such as nucleic acids and enzymes, thus improving antimicrobial activity. Theta defensins in some primates are a good example of cyclic AMPs. They show wide-spectrum action against bacteria, fungi, and enveloped viruses and are highly resistant to thermal and proteolytic degradation [83]. The structural stability, amphipathic nature, and multifunctional activity make cyclic peptides a prime choice for the discovery of next-generation antimicrobial therapeutics. Their peculiarity promises high potential in the fight against multidrug-resistant pathogens and the construction of new peptide-derived drugs that are more potent and stable (Figure 2).

AMP sources are extremely different and include fungi, insects, bacteria, plants, amphibians, and mammals. They play a crucial role in innate immunity. Their natural sources, modern biotechnological, and synthetic production techniques have significantly extended the possibility of obtaining AMPs for therapeutic application. Recombinant DNA technology, solid-phase peptide synthesis, and microbial fermentation are the most common methods for AMP production on an industrial scale, confirming high yield and purity. In direct comparison to conventional antibiotics, the production of AMPs has several advantages: simpler biosynthetic pathways often mean a lower environmental impact, and peptides can be optimized genetically or chemically in ways that reduce cytotoxicity while improving consistency. Cell-free expression systems and bioengineering techniques have moreover enabled the rapid generation of novel AMPs with tailored antimicrobial spectra and physicochemical properties. Taken together, these advances have improved the sustainability and flexibility of the AMP production process while opening perspectives for large-scale industrial production. Thus, feasibility and versatility in the AMP production processes represent promising alternatives to traditional drug development, enabling the solving of economic and resistance-related challenges in modern antimicrobial therapy.

Mammalian AMPs, including cathelicidins and defensins, are part of innate immunity, providing immediate and broad-spectrum protection against microbial pathogens. Cathelicidins, including human LL-37, and defensins (α- and β-defensins) are secreted on epithelial surfaces, within neutrophils, and other immune cells and represent the first line of defence against bacteria, fungi, viruses, and parasites [84]. These peptides are cationic and amphipathic in nature to a large extent, which allows them to selectively engage with the negatively charged microbial membranes without harming the host cells, whose membranes are mostly charge neutral. The major action mechanism of cathelicidins and defensins is membrane targeting. When exposed to microbial membranes, these peptides are able to adopt amphipathic conformations that allow them to insert into the lipid bilayer [85]. They destabilize the membrane through the mechanisms of pore formation (barrel-stave and toroidal pore models) or surface accumulation that causes disintegration of the membrane (carpet model), leading to leakage of the cytoplasmic contents, loss of membrane potential, and quick microbial cell death. In addition to direct membrane disruption, these peptides have non-membrane targeting mechanisms. They can import inside the microbial cells and inhibit intracellular functions such as nucleic acid and protein synthesis [86]. Some defensins also bind lipid II, a pivotal precursor in the synthesis of bacterial cell walls, inhibiting cell wall formation and aiding in microbial killing. Besides their antimicrobial action, mammalian AMPs are involved in modulating host immune responses. LL-37 and defensins have the ability to recruit immune cells, activate cytokine production, and improve wound healing, thus bridging innate immunity to adaptive responses [87]. The synergy of membrane disruption, intracellular targeting, and immunomodulatory activity makes cathelicidins and defensins extremely potent against multidrug-resistant pathogens and a solid platform for the design of new therapeutic approaches. Their structural flexibility, broad-spectrum activity, and immune-regulating functions mark them as promising next-generation antimicrobials (Table 2).

Amphibians, especially frogs, produce a wide variety of AMPs from their skin secretions as an important defense mechanism to combat pathogens in wet, microbe-laden environments. Among these, magainins from Xenopus laevis are one of the best-characterized examples. Magainins are amphipathic, cationic peptides that are known to adopt an α-helical conformation when they interact with microbial membranes [95]. Their amphipathic character allows for selective action against negatively charged microbial membranes, for example, bacterial lipopolysaccharides in Gram-negative bacteria or teichoic acids in Gram-positive bacteria, with relative sparing of mammalian cells because of differences in membrane structure. Membrane targeting is the major mechanism of action of magainins. On binding to the microbial surface, magainins insert into the lipid bilayer and induce toroidal pore formation, where the peptides aggregate and force the membrane to curve inward, creating pores lined by both the peptides and lipid head groups [96]. This leads to leakage of ions, metabolites, and cytoplasmic contents, resulting in swift microbial cell killing. In other cases, at elevated concentrations, magainins are capable of disorganizing membranes through a carpet-like mechanism, in which the surface becomes coated and destabilized in a detergent-like fashion. In addition to direct membrane disruption, magainins can also display other immunomodulatory effects, including augmenting host immune responses and facilitating wound healing [97]. Their wide range of activity against bacteria, fungi, and some viruses, as well as low resistance-inducing capacity, makes magainins very useful templates for the design of synthetic peptides. Magainin structural versatility, membrane selectivity, and multifunctional activity highlight their clinical potential as second-generation antimicrobial drugs, especially against drug-resistant pathogens (Table 3).

Insects generally exploit AMPs as a main defence strategy against microbial infection, due to the lack of an adaptive immune system [104]. Among the most well-studied insect-derived AMPs are cecropins and attacins, which possess broad-spectrum activity against bacteria and fungi. Cecropins are short, cationic, amphipathic α-helical peptides that act on bacterial membranes, while attacins are longer, glycine-rich peptides that mainly target bacterial outer membrane proteins [105]. The mode of action of cecropins is chiefly membrane targeting. The electrostatic interactions of cecropins with the anionic microbial membranes lead to the adoption of α-helical structures following contact. They embed in the lipid bilayer and cause the creation of transmembrane pores that disrupt membrane integrity. This leads to ion leakage and cytoplasmic contents leakage, depolarization, and eventually microbial cell death [106]. Depending on the concentration of peptide and the composition of the membrane, cecropins might also utilize a carpet mechanism, binding to the surface and destabilizing the lipid bilayer in detergent fashion. Attacins interfere with bacterial outer membrane protein synthesis, however. Through their binding to lipopolysaccharides and prevention of the synthesis of certain outer membrane proteins, attacins degrade the structure and permeability of the bacterial envelope, inhibiting growth and increasing sensitivity to host defence mechanisms [107]. Aside from direct antimicrobial action, insect AMPs have the ability to modulate the host immune system by initiating hemocyte recruitment and facilitating phagocytosis. The synergy between quick membrane disintegration (cecropins) and the disruption of crucial bacterial protein synthesis (attacins) makes insect AMPs very effective at regulating microbial numbers [108]. Structural variety, specificity, and low resistance-potentiating propensity all highlight their potential to serve as templates for the design of new antimicrobial drugs against multidrug-resistant pathogens (Table 4).

Plants produce a wide variety of AMPs as a part of their innate immunity to fight microbial pathogens. Thionins and plant defensins are noteworthy examples that protect plant tissues against bacterial, fungal, and viral infections. They are typically small in size, cationic, and cysteine-rich, which allows them to form a stable tertiary structure and selectively bind to microbial cell membranes. Thionins are amphipathic peptides that act primarily by targeting membranes. They electrostatically bind to negatively charged phospholipids in microbial membranes, inserting their hydrophobic ends into the lipid bilayer [115]. This binding disrupts membrane integrity by causing pore formation, leakage of cytoplasmic material, and eventually cell death. The quick mode of action of thionins makes them very potent against a wide range of microorganisms, especially fungi and Gram-positive bacteria. On the other hand, plant defensins have a dual mode of action. Aside from disintegrating microbial membranes like thionins, they also have a specific target within intracellular elements [116]. For example, some plant defensins suppress fungal cell wall biosynthesis by inhibiting glucosylceramide or other essential membrane-associated proteins, interrupting cell growth and division. Plant defensins can also induce reactive oxygen species (ROS) accumulation inside microbial cells to further augment antimicrobial activity. Plant AMPs are stabilized by disulfide bridges, which safeguard them against proteolytic degradation and stress conditions [117]. Their structural stability, broad-spectrum action, and multiplicity of mechanisms make plant AMPs extremely useful for biotechnological purposes, such as the engineering of resistant crops and antimicrobial agents of natural origin. The synergy between membrane disruption, intracellular disruption, and ROS induction highlights the evolutionary value and therapeutic opportunity of peptides from plants in the fight against pathogenic microorganisms (Table 5).

Microorganisms, including bacteria and fungi, produce AMPs called bacteriocins as part of their competitive survival mechanisms under natural conditions. Bacteriocins are ribosomal produced peptides that have strong antimicrobial properties against closely related or rival microbial species [124]. Nisin, which is produced by Lactococcus lactis, Actinobacteria (Streptomyces), and Bacillus, is one of the most well-characterized bacteriocins and is used widely as a natural food additive preservative because of its wide-spectrum activity against Gram-positive bacteria [125]. The mechanism of action of nisin is through the inhibition of cell wall synthesis and membrane disruption. Nisin binds to the lipid II specifically, a precursor molecule in peptidoglycan biosynthesis [126]. Nisin sequesters lipid II, preventing peptidoglycan subunits from being incorporated into the growing bacterial cell wall and causing the loss of cell wall integrity. This inhibition is most lethal for Gram-positive bacteria, where a thick layer of peptidoglycan is essential for survival. Apart from inhibiting cell wall biosynthesis, nisin also causes the formation of membrane pores at regions where lipid II is present. Insertion into the cytoplasmic membrane is promoted by the peptide lipid II complex and results in transient pores that allow small molecules and ions to leak out, causing depolarization and cell death [127]. This two-pronged mechanism, acting on cell wall biosynthesis and membrane integrity, maximizes the bactericidal activity of nisin and reduces the chances of resistance emergence. Bacteriocins like nisin are highly specific and stable owing to post-translational processing and, in certain cases, cyclization. These properties make them prime candidates for therapeutic and commercial uses such as natural preservatives, antimicrobial coatings, and future alternatives to antibiotics [128]. Their multifunctionality, conformational stability, and capacity to hit critical cellular processes highlight the evolutionary and practical importance of microbial AMPs in modulating microbial communities and fighting multi-resistant pathogens (Table 6).

AMPs are a potential new choice to replace traditional antibiotics, especially for the management of multidrug-resistant pathogens. The fast rise in antibiotic resistance, especially due to the overuse and abuse of traditional antibiotics, has made many bacterial infections more difficult to manage [135]. AMPs, by virtue of their novel mechanisms of action, constitute a viable remedy to this major global health challenge. In contrast to traditional antibiotics that frequently attack a single bacterial process, AMPs more often disrupt microbial membranes and, in some cases, affect intracellular activities like nucleic acid synthesis, protein synthesis, or cell wall biosynthesis. Not only does this multi-pronged strategy guarantee speedy eradication of the pathogen, but it also reduces the ability of microorganisms to develop resistance since microorganisms find it difficult to simultaneously develop defences for multiple mechanisms [136]. A number of AMPs are in clinical trials or under investigation for effectiveness against drug-resistant bacteria. For example, human cathelicidin LL-37 shows strong activity against MRSA and Escherichia coli. Defensins, such as α- and β-defensins, also show broad-spectrum activity towards both Gram-positive and Gram-negative bacteria. Engineered synthetic or modified AMPs are also being developed to be more stable, less toxic, and with better pharmacokinetic properties, thus making them more effective for therapeutic use [137]. Beyond their immediate antimicrobial action, certain AMPs exhibit immunomodulatory activity, augmenting host defence through the recruitment of immune cells, induction of cytokine production, and resolution of inflammation. These two activities steer pathogen elimination and immune modulation further to make them promising candidates as next-generation antimicrobial agents [138, 139]. Overall, the promiscuity, wide spectrum effectiveness, and low resistance propensity make AMPs of great worth in the fight against multidrug-resistant infections and in meeting the acute need for new antimicrobial therapies in modern medicine [140].

AMPs are a part of both microbial defence and tissue repair facilitation and wound healing. This LL-37, a human cathelicidin, has been well studied for its antimicrobial activity and roles in immunomodulation [141]. In the process of wound generation, microbial invasion is a major source of infection risk, and this can potentially hinder healing. AMPs like LL-37 rapidly target and eliminate pathogens, such as bacteria, fungi, and viruses, thus avoiding infection and creating a milieu that supports tissue regeneration. In addition to their antimicrobial activity, AMPs also play an active role in immune cell recruitment and modulation. LL-37, for instance, recruits neutrophils, monocytes, and mast cells to the site of injury and promotes pathogen clearance and the inflammatory stage of healing [142]. It also activates keratinocytes, fibroblasts, and endothelial cells, encouraging proliferation, migration, and angiogenesis, vital processes for re-epithelialization and tissue remodelling. AMPs are also able to modulate the production of cytokines, tipping the pro-inflammatory and anti-inflammatory balance against excessive inflammation that could otherwise hinder healing [143]. The multi-functional nature of AMPs can be seen in chronic wounds and diabetic ulcers as well, where malfunctioning immune responses and microbial colonization hinder the process of recovery. The use of AMPs in topical products or hydrogel-based delivery systems has shown enhanced wound closure, diminished microbial load, and enhanced tissue regeneration in animal models [144]. In addition, synthetic and engineered AMPs are under development with increased stability, diminished proteolytic degradation, and optimized activity under difficult wound conditions. In general, the combined antimicrobial, immunomodulatory, and tissue regenerative functions of AMPs make them appealing therapeutic agents for the facilitation of wound healing. Their capacity both to suppress infection and actively induce tissue repair highlights their promise as multifunctional biotherapeutics of clinical medicine and regenerative health care [145].

Medical implants, catheters, and prosthetic devices are widely used in modern medicine but have a high risk of causing infection as a result of microbial colonization and biofilm formation [146]. Biofilms protect pathogens against host immune defences and standard antibiotics, often leading to chronic infections that are difficult to eradicate. AMPs prove to be an attractive option as functional coatings for medical devices with broad-spectrum antimicrobial efficacy and low resistance potential [147]. AMPs may be immobilized or loaded onto device surfaces using several methodologies, such as covalent attachment, layer-by-layer assembly, or encapsulation inside polymer matrices. After application, AMPs dynamically prevent bacterial adhesion and biofilm formation by disrupting microbial membranes upon contact. For instance, cationic and amphipathic peptides bind to negatively charged microbial membranes, promoting pore formation, membrane depolarization, and microbial killing [148]. Acting against early colonizers, AMPs significantly inhibit biofilm formation, ultimately decreasing the risk of device-associated infection, like catheter-associated urinary tract infection (CAUTI) or prosthetic joint infection. In addition to their antimicrobial activity, some AMPs have immunomodulatory and anti-inflammatory activities that can promote tissue integration around the device and support host defence [149]. Coatings with LL-37, human defensins, or synthetic mimetics have been shown to have long-term antimicrobial activity, biocompatibility, and low cytotoxicity in preclinical models. The stability and diversity of AMPs also make it possible to tailor them to target specific devices, with controlled release and extended activity in clinical applications [150]. In general, AMP-based coatings are a novel means of diminishing healthcare-associated infections, enhancing implant safety, and prolonging device longevity. Their ability to integrate direct killing of microorganisms, inhibition of biofilms, and immunomodulation highlights their promise as next-generation products in biomedical device technology [151]. The incorporation of AMPs in medical devices represents an active means of combating multidrug-resistant bacteria and improving patient outcomes.

AMPs, specifically bacteriocins like nisin, are widely used as natural food preservatives in the food industry. The growing need for safe, efficient, and minimally processed foods has increased interest in AMPs because of their low toxicity and wide range of antimicrobial activity. Bacteriocins are ribosomally produced peptides from some bacteria, which may be lactic acid bacteria, to inhibit the growth of other competing microorganisms [151]. Nisin, which is derived from Lactococcus lactis, is perhaps the best characterized and most widely used AMP under these circumstances. The major mode of action of nisin is through disrupting cell membranes and inhibiting cell wall biosynthesis. Nisin interacts with lipid II, a critical precursor in peptidoglycan formation in bacteria, thus inhibiting cell wall development and leading to pore formation in the cytoplasmic membrane [152]. This two-way action leads to the quick killing of bacteria, especially against Gram-positive bacteria like Listeria monocytogenes, Staphylococcus aureus, and Bacillus species. Its efficacy at low concentrations makes nisin a safe and effective preservative for foods of diverse nature, ranging from dairy foods to canned vegetables and processed meats [153]. Besides antimicrobial action, AMPs such as nisin possess some beneficial features over conventional chemical preservatives. They are non-toxic to humans, biodegradable, and are considered generally recognized as safe (GRAS) by regulatory authorities. Their application can minimize the dependence on synthetic preservatives, which tend to be linked with negative health impacts and consumer acceptance issues. Moreover, AMPs can be used with other preservation methods, i.e., mild heat treatment or packaging changes, to enhance synergistic effects and shelf life [154]. In general, AMPs are a natural, efficient, and safe method for food preservation with quality and safety, responding to consumer needs for clean-label products. Their broad activity, low potential for resistance, and synergy with current food processing technologies make them priority bio-preservatives in the changing food industry.

AMPs are also direct antimicrobial agents and powerful immunomodulators with the potential to boost vaccine efficacy [155]. Some AMPs, like human cathelicidin LL-37 and defensins, act as vaccine adjuvants through immune-modulating effects on the host immune system, thus augmenting antigen-specific responses. Such functionality makes AMPs especially promising for the prevention of infectious diseases and therapeutic vaccine development [156]. The immunomodulatory action of AMPs is through several mechanisms, involving the recruitment and activation of numerous immune cells, e.g., dendritic cells, macrophages, and T lymphocytes, to the site of antigen exposure [157–159]. The recruitment facilitates antigen uptake and presentation and consequently triggers the innate and adaptive immune responses. Furthermore, AMPs also induce the release of cytokines and chemokines, including interleukins and interferons, which further augment immune signalling and coordinate an appropriate inflammatory response. Through a regulation of the immune environment, AMPs allow for the induction of a stronger, more durable, and more precise immune response towards the injected antigen [160]. When employed as vaccine adjuvants, AMPs can enhance the immunogenicity of traditional vaccines, such as subunit or inactivated vaccines that otherwise induce poor immune responses. For example, co-administration of LL-37 with protein antigens has been demonstrated to augment antibody responses, T-cell stimulation, and protective immunity in model systems. Additionally, AMPs are of low toxicity and have very low chances of causing adverse reactions, making them safer options compared to conventional adjuvants like aluminium salts [161]. In conclusion, the combination of antimicrobial properties, recruitment of immune cells, and cytokine modulation makes AMPs multifunctional molecules with much potential for vaccine development. Their capacity to boost both innate and adaptive immunity highlights their potential to serve as the next generation of vaccine adjuvants, with innovative treatments for fighting infectious diseases and enhancing global public health outcomes.

AMPs have shown great promise as anti-cancer medicines since they can specifically kill tumor cells while leaving normal healthy cells intact [162]. Cancer cell membranes tend to possess different biochemical properties than normal cells, such as greater negativity in charge, greater membrane fluidity, and greater expression of anionic molecules such as phosphatidylserine and sialic acid. These properties make cancer cells vulnerable to cationic and amphipathic AMPs, which are able to preferentially interact with and destabilize cancer cell membranes [163]. Membrane disruption is the main mechanism of AMP-induced anti-cancer activity. Cationic peptides, including magainins, LL-37, and derivatives of defensin, react with the negatively charged cancer cell membranes, resulting in pore formation, depolarization of the membranes, and leakage of cellular content. This leads to the quick death of cells, usually through necrosis or apoptosis [164]. Certain AMPs also have intracellular actions, such as interference with mitochondrial function, generation of ROS, and disruption of nucleic acid or protein synthesis, which add to selective tumor cell cytotoxicity. Apart from the direct cytotoxicity, AMPs are also capable of altering the tumor microenvironment. Specific peptides also augment anti-tumor immune responses by enlisting immune cells, inducing cytokine secretion, and activating antigen presentation, resulting in synergistic enhanced tumor clearance [165]. The combined activity of AMPs, direct membrane-targeted cytotoxicity, and immunomodulation presents a benefit over traditional chemotherapeutic agents, which tend to have poor specificity and induce systemic toxicity. Synthetic and engineered AMPs are in development with enhanced stability, bioavailability, and target specificity, and they are promising candidates for cancer treatment [166]. Selective killing of cancer cells, a remote chance of resistance occurrence, and multi-targeting mechanisms highlight the therapeutic potential of AMPs as new cancer drugs [167]. Their incorporation into future oncology approaches could serve as add-on treatments to current therapies, providing safer and more effective options in cancer treatment.

AMPs are measured as capable antiviral agents because they can affect several steps of viral infection, including viral entry, replication, and assembly. Unlike typical antivirals, which act by inhibiting some specific enzyme or replication pathways, AMPs work either through direct virucidal action, disruption of viral membranes, or through immune modulation, thus using broad-spectrum antiviral activity. The peptides LL-37, defensins, and lactoferricin have been confirmed to have strong inhibitory actions against both enveloped and non-enveloped viruses [168]. For example, LL-37 disrupts the viral envelope and inhibits attachment to the host cells of influenza and herpes simplex virus, while human β-defensins interfere with human immunodeficiency virus (HIV) replication by blocking viral fusion and reverse transcription [169]. Similarly, indolicidin and magainin-2 exhibit virucidal activity against hepatitis and respiratory viruses. Besides this, AMPs can enhance antiviral immunity by induction of cytokine release and improvement of interferon-mediated defence mechanisms [170]. Structural flexibility agrees modification for increased selectivity and reduced cytotoxicity, important features for therapeutic use. Synthetic and recombinant AMPs are being used as adjuvants in vaccine formulations and topical antiviral agents, mainly in infections at mucosal sites. Low propensity for resistance growth further improves their likely over straight antiviral. Overall, the antiviral effectiveness of AMPs places them as promising candidates for broad-spectrum antiviral therapy, offering new perspectives against emerging and drug-resistant viral pathogens [171].

AMPs have exposed antiparasitic activity against protozoan and helminthic parasites by targeting different modes of action: membrane disruption, inhibition of nutrient uptake, and interference with intracellular signalling pathways. Due to their amphipathic and cationic nature, AMPs can bind negatively charged parasitic membranes, leading to pore formation and following cell lysis [172]. Thus, the best known examples of AMPs are cecropins and magainins, showing strong activity against Plasmodium falciparum, the causative agent of malaria [173]. Dermaseptins isolated from frog skin were found to lyse Leishmania donovani and Trypanosoma cruzi. Other AMPs, such as temporins, act against Giardia lamblia and Toxoplasma gondii [174]. Moreover, AMPs like defensins interact with the host immune response through the induction of macrophage activation, leading to enhanced parasite killing. Their selective toxicity toward parasites over host cells arises from structural differences in the membrane composition and thus discusses a therapeutic advantage. The direct parasiticidal action of AMPs interferes with parasite transmission by targeting vector stages like mosquito gut parasites or helminth larvae and prophylactic potential [175]. Synthetic analogs and logically engineered AMPs are being developed for improved stability and bioavailability under physiological conditions, which would overcome some limitations forced by the degradation of peptides by proteases. Compared to conventional antiparasitic drugs, AMPs exhibit broader activity spectra, rapid action, and reduced likelihood of resistance. Accordingly, AMPs are strong candidates for next-generation antiparasitic drugs against infections whose global burden has recently increased due to drug-resistant malaria, leishmaniasis, and trypanosomiasis [176].

Antifungal properties of AMPs are gaining interest due to the increasingly irritating problem of resistance to conservative antifungal drugs such as azoles and echinocandins. AMPs exert antifungal effects by causing membrane permeabilization, inhibition of cell wall biosynthesis, or interfering with intracellular targets and eventually inducing fungal cell death. For example, histatins derived from human saliva target mitochondria in Candida albicans and induce ROS formation [177]. Defensins and thionins from plants have a wide antifungal spectrum, which encompasses species belonging to Aspergillus, Fusarium, and Cryptococcus [178]. The fungus-derived plectasin interferes with cell wall biosynthesis by binding to lipid II, using a mode of action different from that utilized by the traditional antifungals. The magainins and lactoferricin disrupt fungal membranes by forming transient pores, leading to the leakage of cellular contents [179]. AMPs are also active against biofilms developed by fungal pathogens during device or mucosa-linked infections. More significantly, AMPs were often shown to act synergistically with existing antifungal agents, with fractional inhibitory concentration (FIC) catalogs indicating lower concentrations of the drugs necessary to inhibit growth and hence less toxicity [180]. Immunomodulatory volumes also enhance host defence by employing immune cells and inducing antifungal cytokine production [181]. Multifunctional and adaptable AMPs with their very low tendency to develop resistance represent an excellent class of antifungal therapeutics; systemic and topical formulations can be developed for the treatment of life-threatening, multiresistant fungal infections.

The direct antimicrobial actions of AMPs play an increasingly important role as modulators of the host immune system. They act as immune regulators, bridging innate and adaptive immunity by activating immune cells, modulating cytokine expression, and regulating inflammatory responses. For instance, its antimicrobial properties LL-37 induce chemotaxis of neutrophils, monocytes, and T cells and promotes the production of anti-inflammatory cytokines such as IL-10 [182]. Similarly, defensins increase dendritic cell maturation and antigen presentation, thereby contributing to adaptive immune activation. AMPs like hepcidin and cathelicidins regulate iron metabolism and oxidative stress pivotal for maintaining immune homeostasis. Their ability to modulate TLR signalling pathways enables them to finely inflammatory responses and avoid excessive tissue damage [183]. The synthetic analogs of AMPs are being examined in autoimmune and inflammatory disorders based on their ability to suppress hyperinflammation and promote tissue repair. Additionally, AMPs have been reported to have wound healing and angiogenic properties, thus supporting tissue regeneration in chronic wounds and burns. Unlike other immunomodulators, AMPs have the advantage of directly clearing pathogens and enhancing immune responses without leading to immunosuppression [184]. Their multifunctionality and low resistance potential make them attractive candidates for immunotherapeutic development. The immunomodulatory properties of AMPs extended their role from a mere antimicrobial agent to that of an endogenous regulator of immune balance and tissue homeostasis, opening new avenues for innovative anti-inflammatory and immune supportive therapies [185].