Antimicrobial resistance (AMR) is an ancient phenomenon (D'Costa et al., 2011) where microorganisms have evolved strategies to adapt to diverse environmental niches (Wright, 2007; D'Costa et al., 2011). The widespread use of antibiotics in healthcare and farming has accelerated AMR through natural adaptation and co-evolution, primarily due to the misuse and overuse of traditional antimicrobials (Prestinaci et al., 2015). Today, the phenomenon of AMR is a latent global problem approaching alarming levels that compromise the value of existing treatments in routine clinical practice and their health outcomes. Impacts of AMR will include increased deaths, unmet demand for livestock products, crop losses, and significant economic and social consequences (Ahmad and Khan, 2019; Oniciuc et al., 2019).
Projections for the health sector indicate that the inability to effectively tackle AMR could lead to more than 39 million deaths directly caused by AMR and 169 million deaths related to AMR between 2025 and 2050 (GBD 2021 Antimicrobial Resistance Collaborators, 2024). Healthcare expenditures are expected to increase significantly due to longer hospital stays and extended treatments. Additionally, low- and middle-income countries are likely to experience a substantial economic impact, with a decline in gross domestic product (GDP) exceeding 5 % (GBD 2021 Antimicrobial Resistance Collaborators, 2024; Ho et al., 2024). AMR in livestock and aquaculture is also a growing issue since it can affect animal and human health through the food chain. Notably, over 70 % of antibiotic sales are attributed to their use in animal production for prophylactic purposes and growth promotion (Mehrabi et al., 2020; McNamara and Bomkamp, 2022). The widespread application of pesticides (e.g., bactericides and fungicides) in agriculture has also resulted in negative implications on human health, pollinators, and environmental contamination. In the United States, the economic burden associated with the negative health impacts of pesticide exposure is estimated to exceed US$10 billion annually (Lykogianni et al., 2021).
With fewer novel antimicrobials from the pharmaceutical industry, combating multidrug-resistant microbes is a major scientific, medical, and industrial challenge (Piddock, 2012). The shift in using antimicrobial agents for medicine (e.g., microbial infections, major surgery, organ transplantation, and chemotherapy) to economic sectors (e.g., maintaining health and productivity in livestock production) has increased dependence on antimicrobials (Roope et al., 2019; Caneschi et al., 2023). Projections for 2030 indicate a 67 % rise in antibiotic usage in livestock, a 33 % increase in aquaculture, and an expansion of up to 32 % in human medicine (Baudoin et al., 2021). Despite efforts by different world organizations and public policymakers to develop contingency plans, the discovery of new antimicrobial treatments is more urgent than ever.
Antimicrobial peptides (AMPs) represent a diverse and evolutionarily conserved element of innate immunity, found across multiple life kingdoms (Koehbach and Craik, 2019). In animals, AMPs are produced by skin cells, mucosal surfaces, and immune cells, where they serve as a primary defence mechanism against infectious agents (Sarkar et al., 2021). In plants, AMPs are synthesized as part of their defence responses to bacterial, fungal, and viral pathogens (Shwaiki et al., 2021). Additionally, AMPs produced by fungi and bacteria play a crucial role in protecting these organisms from competing microorganisms, thus aiding in their survival and ecological success (Sugrue et al., 2024). AMPs are seen as an alternative antibiotic modality for the development of leads against pathogens affecting human health and industry (Mejía-Pitta et al., 2021; Torres et al., 2021; Deo et al., 2022; Wan et al., 2024), with ongoing efforts to expand their repertoire. In the Antimicrobial Peptide Database (reviewed on February 13, 2025), 3,306 AMPs isolated from almost all living organisms (bacteria, fungi, mammals, insects, amphibians) have been reported. Furthermore, AMPs display a remarkable diversity of structures and functions. AMPs are frequently less than 50 amino acids typically composed of positively charged and hydrophobic residues (Wan et al., 2024).
Due to their amphiphilic nature, the principal mode of action involves interaction of cationic groups of peptides with negatively charged phospholipids in the cell surface of pathogens, resulting in membrane disruption (Savitskaya et al., 2023). This fast acting mechanism reduces the probability of developing drug resistance (Annunziato and Costantino, 2020). Further, the main target (e.g., membrane) is not directly linked to the genetic code, and therefore in theory, is more difficult for a microbe to evolve resistance mutations (Shukla et al., 2022). AMPs also offer a safer profile (i.e., reduced side effects to host cells) and potent broad-spectrum activity against bacteria, fungi, viruses, parasites, and bioinsecticides. (Windley et al., 2012; Mahlapuu et al., 2016; Annunziato and Costantino, 2020). While AMPs are extensively described in the literature, most studies have focused on their mechanism of action (MOAs) and therapeutic applications in healthcare (Mookherjee et al., 2020). This review aims to highlight advances in AMP applied research, including their multifunctionality, industrial applications, synthesis methods, and market potential, offering insights for their future use in agriculture, aquaculture, farming, and related application fields.
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