Antimicrobial peptides (AMPs) are a class of small peptides that widely exist in nature and they are an important part of the innate immune system of different organisms. AMPs have a wide range of inhibitory effects against bacteria, fungi, parasites and viruses. The emergence of antibiotic-resistant microorganisms and the increasing of concerns about the use of antibiotics resulted in the development of AMPs, which have a good application prospect in medicine, food, animal husbandry, agriculture and aquaculture. This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved. The research progress on antivirus peptides, especially anti-coronavirus (COVID-19) peptides, has been introduced given the COVID-19 pandemic worldwide in 2020.

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Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

Antimicrobial peptides (AMPs), critical components of the innate immune system, are widely distributed throughout the animal and plant kingdoms. They can protect against a broad array of infection-causing agents, such as bacteria, fungi, parasites, viruses, and tumor cells, and also exhibit immunomodulatory activity. AMPs exert antimicrobial activities primarily through mechanisms involving membrane disruption, so they have a lower likelihood of inducing drug resistance. Extensive studies on the structure-activity relationship have revealed that net charge, hydrophobicity, and amphipathicity are the most important physicochemical and structural determinants endowing AMPs with antimicrobial potency and cell selectivity. This review summarizes the recent advances in AMPs development with respect to characteristics, structure-activity relationships, functions, antimicrobial mechanisms, expression regulation, and applications in food, medicine, and animals.

Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era.

Data Repository of Antimicrobial Peptides (DRAMP, http://dramp.cpu-bioinfor.org/ ) is an open-access comprehensive database containing general, patent and clinical antimicrobial peptides (AMPs). Currently DRAMP has been updated to version 2.0, it contains a total of 19,899 entries (newly added 2,550 entries), including 5,084 general entries, 14,739 patent entries, and 76 clinical entries. The update covers new entries, structures, annotations, classifications and downloads. Compared with APD and CAMP, DRAMP contains 14,040 (70.56% in DRAMP) non-overlapping sequences. In order to facilitate users to trace original references, PubMed_ID of references have been contained in activity information. The data of DRAMP can be downloaded by dataset and activity, and the website source code is also available on dedicatedly designed download webpage. Although thousands of AMPs have been reported, only a few parts have entered clinical stage. In the paper, we described several AMPs in clinical trials, including their properties, indications and clinicaltrials.gov identifiers. Finally, we provide the applications of DRAMP in the development of AMPs.

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DRAMP 2.0, an updated data repository of antimicrobial peptides

Topical antimicrobial peptide formulations for wound healing: Current developments and future prospects

The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.

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Antimicrobial peptides: mechanism of action, activity and clinical potential.

Poor proteolytic resistance is an urgent problem to be solved in the clinical application of antimicrobial peptides (AMPs), yet common solutions, such as complicated chemical modifications and utilization of d-amino acids, greatly increase the difficulty and cost of producing AMPs. In this work, a set of novel peptides was synthesized based on an antitrypsin/antichymotrypsin hydrolytic peptide structure unit (XYPX)n (X represents I, L, and V; Y represents R and K), which was designed using a systematic natural amino acid arrangement. Of these peptides, 16 with seven repeat units had the highest average selectivity index (GMSI = 99.07) for all of the Gram-negative bacteria tested and remained highly effective in combating Escherichia coli infection in vivo. Importantly, 16 also had dramatic resistance to a high concentration of trypsin/chymotrypsin hydrolysis and exerted bactericidal activity through a membrane-disruptive mechanism. Overall, these findings provide new approaches for the development of anti...

Antimicrobial Peptides with High Proteolytic Resistance for Combating Gram-Negative Bacteria

Antimicrobial peptides are an important weapon against invading pathogens and are potential candidates as novel antibacterial agents, but their antifungal activities are not fully developed. In this study, a set of imperfectly amphipathic peptides was developed based on the imperfectly amphipathic palindromic structure Rn(XRXXXRX)Rn (n = 1, 2; X represents L, I, F, or W), and the engineered peptides exhibited high antimicrobial activities against all fungi and bacteria tested (including fluconazole-resistant Candida albicans), with geometric mean (GM) MICs ranging from 2.2 to 6.62 μM. Of such peptides, 13 (I6) (RRIRIIIRIRR-NH2) that was Ile rich in its hydrophobic face had the highest antifungal activity (GMfungi = 1.64 μM) while showing low toxicity and high salt and serum tolerance. It also had dramatic LPS-neutralizing propensity and a potent membrane-disruptive mechanism against microbial cells. In summary, these findings were useful for short AMPs design to combat the growing threat of drug-resistant...

Combating Drug-Resistant Fungi with Novel Imperfectly Amphipathic Palindromic Peptides

Coiled-coil, a basic folding pattern of native proteins, was previously demonstrated to be associated with the specific spatial recognition, association, and dissociation of proteins and can be used to perfect engineering peptide model. Thus, in this study, a series of amphiphiles composed of heptads repeats with coiled-coil structures was constructed, and the designed peptides exhibited a broad spectrum of antimicrobial activities. Circular dichroism and biological assays showed that the heptad repeats and length of the linker between the heptads largely influenced the amphiphile’s helical propensity and cell selectivity. The engineered amphiphiles were also found to efficiently reduce sessile P. aeruginosa biofilm biomass, neutralize endotoxins, inhibit the inflammatory response, and remain active under physiological salt concentrations. In summary, these findings are helpful for short AMP design with a highly therapeutic index to treat bacteria-induced infection.

Novel Design of Heptad Amphiphiles To Enhance Cell Selectivity, Salt Resistance, Antibiofilm Properties and Their Membrane-Disruptive Mechanism

Inflammatory bowel disease (IBD) develops as a result of complicated interactions between genetic susceptibility, excessive innate immunity, and environmental factors, which are mainly related to the gut microbiota The present study aimed to elucidate the protective effects and underlying mechanisms of a short-chain fatty acid salt, sodium butyrate, on colonic inflammation induced by dextran sulfate sodium (DSS) in mice Pretreatment with sodium butyrate attenuated colitis, as demonstrated by the decreased disease activity index (DAI), colon length shortening, spleen tumidness, and histopathology scores, while maintaining intestinal barrier integrity, as observed by H&E staining and electron microscopy 16S rRNA sequence analysis revealed that sodium butyrate caused a remarkable alteration of the gut microbiota Bacteroides, Lachnospiraceae, the Lachnospiraceae NK4A136 group, and Ruminiclostridium 6 presented dramatic differences after sodium butyrate supplementation This work verifies that sodium butyrate can improve mouse colitis via microbe–host interactions by regulating the microbial community Taken together, the findings demonstrate that sodium butyrate shows great potential as a probiotic agent for ameliorating colitis

Xiujing Dou

Papers

Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era.

Antimicrobial Peptides with High Proteolytic Resistance for Combating Gram-Negative Bacteria

Combating Drug-Resistant Fungi with Novel Imperfectly Amphipathic Palindromic Peptides

Novel Design of Heptad Amphiphiles To Enhance Cell Selectivity, Salt Resistance, Antibiofilm Properties and Their Membrane-Disruptive Mechanism

Sodium Butyrate Alleviates Mouse Colitis by Regulating Gut Microbiota Dysbiosis.