DRAMP: a comprehensive data repository of antimicrobial peptides

Fan, Linlin; Sun, Jian; Zhou, Meifeng; Zhou, Jie; Lao, Xingzhen; Zheng, Heng; Xu, Hong‐Xi

doi:10.1038/srep24482

Cited by 169 publications

(165 citation statements)

References 36 publications

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“…However, it would appear to be a matter of historical fact that what was most likely the first AMP to be reported from eukaryotes showed a pH dependent mode of action [24,25]. Since these earlier studies, it is now known that these peptides are produced by virtually all multicellular organisms [92,93] and that an increasing number of these molecules possess pH-dependent activity (Table 3). …”

Section: An Overview Of Ph Dependent Peptides and Proteins With Anmentioning

confidence: 99%

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

et al. 2016

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Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era.

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Section: An Overview Of Ph Dependent Peptides and Proteins With Anmentioning

confidence: 99%

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

et al. 2016

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“…In 2018, there were a total of 4849 AMPs based on the DRAMP (data repository of AMPs) database . It consists of 4256 natural peptides and 593 synthetic peptides.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial peptides under clinical investigation

2019

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Overuse of conventional antibiotics as well as the slow pace of new antibiotic drug development leads to antimicrobial resistance (AMR). Because infections with multi‐drug resistant (MDR) pathogens have become a public health issue, the need for a novel class of antibiotics is urgent. Recently, antimicrobial peptides (AMPs) have emerged as a promising platform to fight against MDR bacteria ensuring broad‐spectrum antimicrobial activity and relatively low resistance emergence. Currently, a number of AMPs are undergoing clinical and preclinical trials against various infectious diseases. This review lists the 36 AMPs (27 clinical and 9 preclinical) with brief information about their origin, structure, mechanism, and development status. From the examples of AMPs under clinical investigation, we categorized several improvement strategies and highlighted directions for the future design of AMPs.

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“…Several online databases catalog AMPs: The APD3 database maintained at the University of Nebraska (Wang et al 2016) contains >2,500 peptides, and a recently launched data repository of antimicrobial peptides (accessed 10/2016) contains 17,360 sequences, including 4,582 general AMPs, 12,704 patented sequences, and 74 peptides in drug development (Fan et al 2016). An AMP database restricted to peptides with antibiofilm activity contains about 200 entries (Di Luca et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial Peptides: Mechanisms of Action and Resistance

2016

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More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral cavity. These AMPs have been organized into 6 functional groups, 1 of which, cationic AMPs, has received extensive attention in recent years for their promise as potential antibiotics. The goal of this review is to describe recent advances in our understanding of the diverse mechanisms of action of cationic AMPs and the bacterial resistance against these peptides. The recently developed peptide GL13K is used as an example to illustrate many of the discussed concepts. Cationic AMPs typically exhibit an amphipathic conformation, which allows increased interaction with negatively charged bacterial membranes. Peptides undergo changes in conformation and aggregation state in the presence of membranes; conversely, lipid conformation and packing can adapt to the presence of peptides. As a consequence, a single peptide can act through several mechanisms depending on the peptide's structure, the peptide:lipid ratio, and the properties of the lipid membrane. Accumulating evidence shows that in addition to acting at the cell membrane, AMPs may act on the cell wall, inhibit protein folding or enzyme activity, or act intracellularly. Therefore, once a peptide has reached the cell wall, cell membrane, or its internal target, the difference in mechanism of action on gram-negative and gram-positive bacteria may be less pronounced than formerly assumed. While AMPs should not cause widespread resistance due to their preferential attack on the cell membrane, in cases where specific protein targets are involved, the possibility exists for genetic mutations and bacterial resistance. Indeed, the potential clinical use of AMPs has raised the concern that resistance to therapeutic AMPs could be associated with resistance to endogenous host-defense peptides. Current evidence suggests that this is a rare event that can be overcome by subtle structural modifications of an AMP.

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DRAMP: a comprehensive data repository of antimicrobial peptides

Cited by 169 publications

References 36 publications

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

Antimicrobial peptides under clinical investigation

Antimicrobial Peptides: Mechanisms of Action and Resistance

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