Antimicrobial peptides (AMPs) are regarded as a new generation of antibiotics. Besides antimicrobial activity, AMPs also have antibiofilm, immune-regulatory, and other activities. Exploring the ...mechanism of action of AMPs may help in the modification and development of AMPs. Many studies were conducted on the mechanism of AMPs. The present review mainly summarizes the research status on the antimicrobial, anti-inflammatory, and antibiofilm properties of AMPs. This study not only describes the mechanism of cell wall action and membrane-targeting action but also includes the transmembrane mechanism of intracellular action and intracellular action targets. It also discusses the dual mechanism of action reported by a large number of investigations. Antibiofilm and anti-inflammatory mechanisms were described based on the formation of biofilms and inflammation. This study aims to provide a comprehensive review of the multiple activities and coordination of AMPs
, and to fully understand AMPs to realize their therapeutic prospect.
The concept of antimicrobial peptides (AMPs) as potent pharmaceuticals is firmly established in the literature, and most research articles on this topic conclude by stating that AMPs represent ...promising therapeutic agents against bacterial and fungal pathogens. Indeed, early research in this field showed that AMPs were diverse in nature, had high activities with low minimal inhibitory concentrations, had broad spectrums of activity against bacterial, fungal and viral pathogens, and could easily be manipulated to alter their specificities, reduce their cytotoxicities and increase their antimicrobial activities. Unfortunately, commercial development of these peptides, for even the simplest of applications, has been very limited. With some peptides there are obstacles with their manufacture, in vivo efficacy and in vivo retention. More recently, the focus has shifted. Contemporary research now uses a more sophisticated approach to develop AMPs that surmount many of these prior obstacles. AMP mimetics, hybrid AMPs, AMP congeners, cyclotides and stabilised AMPs, AMP conjugates and immobilised AMPs have all emerged with selective or ‘targeted’ antimicrobial activities, improved retention, or unique abilities that allow them to bind to medical or industrial surfaces. These groups of new peptides have creative medical and industrial application potentials to treat antibiotic-resistant bacterial infections and septic shock, to preserve food or to sanitise surfaces both in vitro and in vivo.
Antimicrobial peptides (AMPs) are distributed across all kingdoms of life and are an indispensable component of host defenses. They consist of predominantly short cationic peptides with a wide ...variety of structures and targets. Given the ever-emerging resistance of various pathogens to existing antimicrobial therapies, AMPs have recently attracted extensive interest as potential therapeutic agents. As the discovery of new AMPs has increased, many databases specializing in AMPs have been developed to collect both fundamental and pharmacological information. In this review, we summarize the sources, structures, modes of action, and classifications of AMPs. Additionally, we examine current AMP databases, compare valuable computational tools used to predict antimicrobial activity and mechanisms of action, and highlight new machine learning approaches that can be employed to improve AMP activity to combat global antimicrobial resistance.
Antimicrobial peptides (AMPs) potentially serve as ideal antimicrobial agents for the treatment of polymicrobial abdominal infections due to their broad‐spectrum antimicrobial activity and excellent ...biocompatibility. However, the balance of chain length, positive charges, and hydrophobicity on the antimicrobial activity of AMPs are still far from being optimal. Herein, a series of AMPs (KXn‐NH2, X = Ile, Leu or Phe, n = 3, 4, 5, or 6) with varied charges and hydrophobicity for the treatment of polymicrobial abdominal infections are designed. Specifically, KI4‐NH2 peptide exhibits the best in vitro antimicrobial activity against Gram‐positive and ‐negative bacteria, as well as fungal strains. Based on the good cell biocompatibility, KI4‐NH2 peptide is found to have negligible in vivo toxicity at the dosage of up to 28 mg kg−1. Furthermore, great in vivo therapeutic efficacy of KI4‐NH2 peptide against S. typhimurium is demonstrated in the mice abdominal infection model. The design of short sequence of antimicrobial peptides with a charge/hydrophobicity balanced structures provides a simple and efficient strategy for potential clinical applications of antimicrobial peptide‐based biomaterials in a variety of bacterial infection diseases.
A charge/hydrophobicity balanced antimicrobial peptide (KI4‐NH2) is optimized for the treatment of polymicrobial abdominal infections. KI4‐NH2 not only has a simple and short sequence to minimize the high production cost, but also has good broad‐spectrum antimicrobial activity and biosafety against bacteria and fungi in vivo and in vitro.
Insects are one of the major sources of antimicrobial peptides/proteins (AMPs). Since observation of antimicrobial activity in the hemolymph of pupae from the giant silk moths Samia Cynthia and ...Hyalophora cecropia in 1974 and purification of first insect AMP (cecropin) from H. cecropia pupae in 1980, over 150 insect AMPs have been purified or identified. Most insect AMPs are small and cationic, and they show activities against bacteria and/or fungi, as well as some parasites and viruses. Insect AMPs can be classified into four families based on their structures or unique sequences: the α-helical peptides (cecropin and moricin), cysteine-rich peptides (insect defensin and drosomycin), proline-rich peptides (apidaecin, drosocin, and lebocin), and glycine-rich peptides/proteins (attacin and gloverin). Among insect AMPs, defensins, cecropins, proline-rich peptides, and attacins are common, while gloverins and moricins have been identified only in Lepidoptera. Most active AMPs are small peptides of 20–50 residues, which are generated from larger inactive precursor proteins or pro-proteins, but gloverins (~14 kDa) and attacins (~20 kDa) are large antimicrobial proteins. In this mini-review, we will discuss current knowledge and recent progress in several classes of insect AMPs, including insect defensins, cecropins, attacins, lebocins and other proline-rich peptides, gloverins, and moricins, with a focus on structural-functional relationships and their potential applications.
The second volume of the Special Issue entitled “Antimicrobial Prescribing and Stewardship” consists of manuscripts, including original research articles, review articles, and opinion papers ...regarding antimicrobial stewardship-related topics, including disease-based/organism-based antimicrobial stewardship; the influence of antimicrobial utilization changes on antimicrobial resistance; the impact of antimicrobial stewardship on quality performance measures and patient outcomes; novel antimicrobial stewardship education and training approaches or interventions aimed toward the public and/or healthcare workers; behavioral change approaches to antimicrobial stewardship; collaborative practice agreements in antimicrobial stewardship; antimicrobial stewardship in special populations (e.g., pediatrics, geriatrics, emergency medicine, hematology/oncology); tackling AMR through antimicrobial stewardship in low- and middle-income countries; antimicrobial stewardship for animal health; antimicrobial stewardship in alternative settings (e.g., community practice, long-term care, resource-limited settings, small and rural hospitals); antimicrobial use and stewardship in the context of the COVID-19 pandemic; and global collaborations to tackle AMR through antimicrobial stewardship.
Antimicrobial peptides (AMPs) are promising alternative agents for antibiotics to overcome antibiotic resistance problems. But, it is difficult to produce large-scale antimicrobial research due to ...the toxicity towards expression hosts or degradation by peptidases in the host. Therefore, heterologous recombinant expression of antimicrobial peptides has always been a challenging issue.
To overcome toxicity to the expression host and low expression level, a new photocleavable protein fusion expression method for antimicrobial peptides is provided.3 Methods: Through directed evolution and high throughput screening, a photocleavable protein mutant R6-2-6-4 with a higher photocleavage efficiency was obtained. The DNA coding sequence of antimicrobial peptide Histatin 1 was fused within the sequence of R6-2-6-4 gene. The fusion gene was successfully expressed in
expression system.
Antimicrobial peptide Histatin 1 could be successfully expressed and purified by fusing within PhoCl mutant R6-2-6-4. The antimicrobial activity was rarely affected, and the MIC value was 33 ug/mL, which was basically equivalent to 32 ug/mL of the chemically synthesized Histatin 1. After amplification in a 5 L fermenter, the expression of PhoCl mutant (R6-2-6-4)-Histatin1 improved up to 87.6 mg/L in fermenter, and Histatin1 obtained by photocleavage also could up to 11 mg/L. The prepared Histatin1 powder remained stable when stored at 4oC for up to 4 months without any degradation. In addition, the expression and photocleavage of β -Defensin105 and Lysostaphin verified the certain universality of the PhoCl mutant fusion expression system.
Antimicrobial peptides Histatin 1, β -Defensin 105 and Lysostaphin were successfully expressed and purified by photocleavable protein mutant. This may provide a novel strategy to express and purify antimicrobial peptides in the
expression system.
Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), are important effector immune defense molecules in multicellular organisms. AMPs exert their antimicrobial activities ...through several mechanisms; thus far, induction of drug resistance through AMPs has been regarded as unlikely. Therefore, they have great potential as new generation antimicrobial agents. To date, more than 30 AMP‐related drugs are in the clinical trial phase. In recent years, studies show that some AMPs and conventional antibiotics have synergistic effects. The combined use of AMPs and antibiotics can kill drug‐resistant pathogens, prevent drug resistance, and significantly improve the therapeutic effects of antibiotics. In this review, we discuss the progress in synergistic studies on AMPs and conventional antibiotics. An overview of the current understanding of the functional scope of AMPs, ongoing clinical trials, and challenges in the development processes are also presented.
Antibiotic resistance is projected as one of the greatest threats to human health in the future and hence alternatives are being explored to combat resistance. Antimicrobial peptides (AMPs) have ...shown great promise, because use of AMPs leads bacteria to develop no or low resistance. In this review, we discuss the diversity, history and the various mechanisms of action of AMPs. Although many AMPs have reached clinical trials, to date not many have been approved by the US Food and Drug Administration (FDA) due to issues with toxicity, protease cleavage and short half-life. Some of the recent strategies developed to improve the activity and biocompatibility of AMPs, such as chemical modifications and the use of delivery systems, are also reviewed in this article.
Bacterial infections caused by 'superbugs' are increasing globally, and conventional antibiotics are becoming less effective against these bacteria, such that we risk entering a post-antibiotic era. ...In recent years, antimicrobial peptides (AMPs) have gained significant attention for their clinical potential as a new class of antibiotics to combat antimicrobial resistance. In this review, we discuss several facets of AMPs including their diversity, physicochemical properties, mechanisms of action, and effects of environmental factors on these features. This review outlines various chemical synthetic strategies that have been applied to develop novel AMPs, including chemical modifications of existing peptides, semi-synthesis, and computer-aided design. We will also highlight novel AMP structures, including hybrids, antimicrobial dendrimers and polypeptides, peptidomimetics, and AMP-drug conjugates and consider recent developments in their chemical synthesis.
This review discusses the diversity of structure and physicochemical properties of antimicrobial peptides and their derivatives, various chemical synthetic strategies that have been applied in their development, and how this links to their activity.
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