Title:Mammalian Antimicrobial Peptides: Promising Therapeutic Targets Against Infection and Chronic Inflammation
Volume: 16
Issue: 1
Author(s): Pujarini Dutta and Santasabuj Das
Affiliation:
Keywords:
AMPs, Cathelicidins, Defensins, IDRs, Infection, Inflammation, Synthetic AMPs.
Abstract: Antimicrobial peptides (AMPs) are integral components of the host innate immune system
and functional throughout the plant and animal kingdoms. AMPs are short cationic molecules and lethal
against a wide range of bacteria, viruses, fungi, yeast and protozoa due to their membranolytic effects
on the negatively-charged microbial membranes. In addition, they exert multiple
immunomodulatory roles like chemotaxis, modulation of cytokine and chemokine expression,
leukocyte activation etc. Since AMPs suffer loss of microbicidal properties under serum and tissue
environments, their capacity to modulate the immune system may predominates under the
physiological conditions. Discovery of new antibiotics is lagging far behind the rapidly spreading drug resistance among
the microorganisms. Both natural and synthetic AMPs have shown promise as ‘next generation antibiotics’ due to their
unique mode of action, which minimises the chance of development of microbial resistance. In addition, they have
therapeutic potential against non-infectious diseases like chronic inflammation and cancer. Many of the synthetic AMPs
are currently undergoing clinical trials for the treatment of debilitating diseases, such as catheter-related infections,
diabetic foot ulcers, chemotherapy-associated infections etc. Some of them have already entered the market as topical
preparations. In this review, we synopsise the current literature of natural and synthetic AMPs in different infectious and
inflammatory diseases of human microfloral habitats, especially the gastrointestinal, respiratory and genitourinary tracts
and the skin. We also discuss the classification of AMPs, their mode action and antimicrobial spectrum, including the
pathogen evasion mechanisms. In short, we tried to present the locus standi of AMPs in relation to human diseases and
highlight the most promising synthetic peptides emerging from the clinical trials. Finally, we focused on the limitations
and hurdles in terms of cost of production, bioavailability, pharmacokinetic stability and toxicity faced by commercial
development and clinical use of the AMPs and strategies to overcome these hurdles.
