The Development of Antimicrobial Peptides as New Antibacterial Drugs

Roscia, Giulia; Falciani, Chiara; Bracci, Luisa; Pini, Alessandro

doi:10.2174/138920371408131227155308

Cited by 45 publications

(40 citation statements)

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“…CLS001 is an AMP that is currently under investigation in a Phase III clinical trial 17,18. In this study, we evaluated the in vitro antimicrobial activities of gentamicin (GEN), amoxicillin (AMO), azithromycin (AZT), and vancomycin (VAN), alone and in combination with DP7 or CLS001, against antibiotic-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii , and Escherichia coli strains.…”

Section: Introductionmentioning

confidence: 99%

Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria

Wu¹,

Li²,

Li³

et al. 2017

DDDT

119

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Antibiotic-resistant bacteria present a great threat to public health. In this study, the synergistic effects of antimicrobial peptides (AMPs) and antibiotics on several multidrug-resistant bacterial strains were studied, and their synergistic effects on azithromycin (AZT)-resistance genes were analyzed to determine the relationships between antimicrobial resistance and these synergistic effects. A checkerboard method was used to evaluate the synergistic effects of AMPs (DP7 and CLS001) and several antibiotics (gentamicin, vancomycin [VAN], AZT, and amoxicillin) on clinical bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli). The AZT-resistance genes (ermA, ermB, ermC, mefA, and msrA) were identified in the resistant strains using quantitative polymerase chain reaction. For all the clinical isolates tested that were resistant to different antibiotics, DP7 had high antimicrobial activity (≤32 mg/L). When DP7 was combined with VAN or AZT, the effect was most frequently synergistic. When we studied the resistance genes of the AZT-resistant isolates, the synergistic effect of DP7–AZT occurred most frequently in highly resistant strains or strains carrying more than two AZT-resistance genes. A transmission electron microscopic analysis of the S. aureus strain synergistically affected by DP7–AZT showed no noteworthy morphological changes, suggesting that a molecular-level mechanism plays an important role in the synergistic action of DP7–AZT. AMP DP7 plus the antibiotic AZT or VAN is more effective, especially against highly antibiotic-resistant strains.

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Section: Introductionmentioning

confidence: 99%

Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria

Wu¹,

Li²,

Li³

et al. 2017

DDDT

119

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“…The second is linked to the generally short half‐life of peptides in vivo. These are the main reasons why among the hundreds of AMPs investigated and developed for application in clinical practice in the last 10 years, only a few have reached the market . Very few examples of branched or dendrimeric AMPs have actually been studied.…”

Section: Branched Peptide Applicationsmentioning

confidence: 99%

“…In the 1980s, cardiovascular medicine and infertility were the primary therapeutic areas for peptide development. Since 2010, peptide drugs that enter human clinical trials have mainly been used in metabolic diseases and oncology, but peptide therapeutics have been tested in a variety of other applications, including gastrointestinal disorders, neurodegenerative diseases, and infectious diseases, such as HIV and bacterial infections . Most approved peptide‐based therapies are directed at extracellular targets; for example, glucagon‐like peptide 1 (GLP‐1) agonists have had great commercial success in diabetes and obesity .…”

Section: Introductionmentioning

confidence: 99%

Branched peptides as bioactive molecules for drug design

et al. 2018

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Peptides are regarded as good candidates for new biotherapeutics in medicine. Several peptides have already completed clinical development, with more than 60 peptide‐based drugs already on the market, and a further 500 derivatives currently in developmental stages. Branched peptides are an emerging class of synthetic molecules being assessed for drug development. Here, we review possible clinical uses of branched peptides, considering major features such as stability, half‐life, toxicity, and efficacy compared to monomeric peptides, biodistribution, as well as modifications, encapsulation, and conjugation to improve delivery or bypass drug resistance. We focus in particular on the use of branched peptides in oncology and infectious diseases.

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“…Several AMPs of natural and synthetic origin are currently being developed preclinically or clinically as new therapeutic agents for systemic, lung, and wound infections (3, 4). The growing interest in such molecules is due to the increase in bacterial multidrug resistance to traditional antibiotics and associated expectations of imminent increased medical need.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory and Anti-inflammatory Activity in Vitro and in Vivo of a Novel Antimicrobial Candidate

Brunetti

Roscia

Lampronti

et al. 2016

Journal of Biological Chemistry

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The synthetic antimicrobial peptide SET-M33 has strong activity against bacterial infections caused by Gram-negative bacteria. It is currently in preclinical development as a new drug to treat lung infections caused by Gram-negative bacteria. Here we report its strong anti-inflammatory activity in terms of reduced expression of a number of cytokines, enzymes, and signal transduction factors involved in inflammation triggered by LPS from Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Sixteen cytokines and other major agents involved in inflammation were analyzed in macrophages and bronchial cells after stimulation with LPS and incubation with SET-M33. The bronchial cells were obtained from a cystic fibrosis patient. A number of these proteins showed up to 100% reduction in expression as measured by RT-PCR, Western blotting, or Luminex technology. LPS neutralization was also demonstrated in vivo by challenging bronchoalveolar lavage of SET-M33-treated mice with LPS, which led to a sharp reduction in TNF-α with respect to non-SET-M33-treated animals. We also describe a strong activity of SET-M33 in stimulating cell migration of keratinocytes in wound healing experiments in vitro, demonstrating a powerful immunomodulatory action generally characteristic of molecules taking part in innate immunity.

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The Development of Antimicrobial Peptides as New Antibacterial Drugs

Cited by 45 publications

References 0 publications

Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria

Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria

Branched peptides as bioactive molecules for drug design

Immunomodulatory and Anti-inflammatory Activity in Vitro and in Vivo of a Novel Antimicrobial Candidate

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