Antimicrobial peptides

About: Antimicrobial peptides is a research topic. Over the lifetime, 10645 publications have been published within this topic receiving 507688 citations. The topic is also known as: host defense peptide & antimicrobial protein.

Cathelicidin LL‐37 induces the generation of reactive oxygen species and release of human α‐defensins from neutrophils

Abstract: Summary Background Psoriasis is characterized by epidermal infiltration of neutrophils that destroy invading microorganisms via a potent antimicrobial arsenal of oxidants and antimicrobial agents. In contrast to atopic dermatitis, psoriasis exhibits low levels of skin infections due to the presence of antimicrobial agents, including cathelicidin LL-37. LL-37 kills a broad spectrum of microbes, and activates neutrophil chemotaxis. Objective To determine whether or not LL-37 could regulate additional neutrophil functions such as production of cytokines/chemokines, reactive oxygen species and release of neutrophil antimicrobial peptides. Methods Human peripheral blood neutrophils were used in this study. The production of interleukin (IL)-8 and release of α-defensins were analysed by enzyme-linked immunosorbent assay, and real-time polymerase chain reaction (PCR) was used to quantify α-defensin gene expression. Phosphorylation of mitogen-activated protein kinase (MAPK) was determined by Western blotting. The generation of reactive oxygen species was examined using flow cytometry, and intracellular Ca2+ mobilization was measured using a calcium assay kit. Results LL-37 enhanced the production of IL-8 under the control of MAPK p38 and extracellular signal regulated kinase (ERK), as evidenced by the inhibitory effects of p38 and ERK1/2 inhibitors on LL-37-mediated IL-8 production. Furthermore, LL-37 induced phosphorylation of p38 and ERK. We also revealed that LL-37 stimulated the generation of reactive oxygen species dose- and time-dependently, most probably via NADPH oxidase activation and intracellular Ca2+ mobilization. Finally, LL-37 induced both mRNA expression and protein release of α-defensins, known as human neutrophil peptide 1–3. Conclusion Taken together, we suggest that in addition to its microbicidal properties, LL-37 may contribute to innate immunity by enhancing neutrophil host defence functions at inflammation and/or infection sites.

Antimicrobial peptides: therapeutic potential

Abstract: A significant component of the innate immune system of a wide variety of animals and plants is arbitrated by cationic host defence peptides. In man, these peptides, in addition to exhibiting a direct antimicrobial activity, seems to provide a range of non-antimicrobial bioactivities related to defence, inflammation and wound healing. Despite the fact that such peptides have so far failed to reach the market, there are continued initiatives to advance such potential therapeutics to, and through, the clinic. The reasons behind such initiatives include: reduced manufacturing costs for peptides; allowing entry into therapeutic areas previously inaccessible due to cost; the continued identification of previously unknown bioactivities of such peptides; and the resurgence of interest in peptide therapeutics. As a result, clinical programmes based on cationic host defence peptides exist in the areas of infection, dermatology, cancer and inflammation. The probability of clinical success for host defence peptide-based therapeutics is on the rise as options for a wider range of clinical indications emerge.

Cationic antimicrobial peptides: towards clinical applications

Abstract: Cationic antimicrobial peptides are important components of the innate immune defences of all species of life. Variants of these natural molecules have a broad range of antibiotic, antifungal, antiviral and anti-endotoxic activity. Two of these cationic peptides have shown signs of efficacy in early clinical trials of oral mucositis and the sterilisation of central venous catheters, respectively and are currently proceeding through Phase III clinical trials. Thus, cationic antimicrobial peptides are currently being investigated as topical agents. In addition, the cationic protein rBPI 21 has recently completed Phase III clinical trials of parenteral use for meningococcaemia.

Population trends associated with skin peptide defenses against chytridiomycosis in Australian frogs.

Abstract: Many species of amphibians in the wet tropics of Australia have experienced population declines linked with the emergence of a skin-invasive chytrid fungus, Batrachochytrium dendrobatidis. An innate defense, antimicrobial peptides produced by granular glands in the skin, may protect some species from disease. Here we present evidence that supports this hypothesis. We tested ten synthesized peptides produced by Australian species, and natural peptide mixtures from five Queensland rainforest species. Natural mixtures and most peptides tested in isolation inhibited growth of B. dendrobatidis in vitro. The three most active peptides (caerin 1.9, maculatin 1.1, and caerin 1.1) were found in the secretions of non-declining species (Litoria chloris, L. caerulea, and L. genimaculata). Although the possession of a potent isolated antimicrobial peptide does not guarantee protection from infection, non-declining species (L. lesueuri and L. genimaculata) inhabiting the rainforest of Queensland possess mixtures of peptides that may be more protective than those of the species occurring in the same habitat that have recently experienced population declines associated with chytridiomycosis (L. nannotis, L. rheocola, and Nyctimystes dayi). This study demonstrates that in vitro effectiveness of skin peptides correlates with the degree of decline in the face of an emerging pathogen. Further research is needed to assess whether this non-specific immune defense may be useful in predicting disease susceptibility in other species.

The antimicrobial peptide ZY4 combats multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii infection.

Abstract: The emergence of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa raises fears of untreatable infections and poses the greatest health threats. Antimicrobial peptides (AMPs) are regarded as the most ideal solution to this menace. In this study, a set of peptides was designed based on our previously reported peptide cathelicidin-BF-15, and the lead peptide ZY4, a cyclic peptide stabilized by a disulfide bridge with high stability in vivo (the half-life is 1.8 h), showed excellent activity against P. aeruginosa and A. baumannii, including standard and clinical multidrug-resistant (MDR) strains. ZY4 killed bacteria by permeabilizing the bacterial membrane and showed low propensity to induce resistance, exhibited biofilm inhibition and eradication activities, and also killed persister cells. Notably, administration of ZY4 decreased susceptibility to lung infection by P. aeruginosa and suppressed dissemination of P. aeruginosa and A. baumannii to target organs in a mouse septicemia infection model. These findings identify ZY4 as an ideal candidate against MDR bacterial infections.