Antimicrobial peptides (AMPs) as drug candidates: a patent review (2003–2015)

Kosikowska, Paulina; Lesner, Adam

doi:10.1080/13543776.2016.1176149

Cited by 139 publications

(108 citation statements)

References 63 publications

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“…In regard to F2.3S and as predicted by in silico analysis, this peptide also presented a potent antibacterial activity against both E. coli and S. aureus reference cultures (Table 2). Moreover, along with their high and potential spectrum antibacterial capability, the new molecules must comply a low toxicity for human cells before considering their medical use [1]. Our findings discard any significant toxicity of BF2 and F2.3S on human primary monocytes at the highest tested concentration.…”

Section: Discussionmentioning

confidence: 60%

“…AMPs are predominantly cationic and contain a high percentage of hydrophobic residues. These features confer structural characteristics to the peptides that define their biological activity and mechanisms of action, as well as represent a basis of new useful natural antibiotics for pharmaceutical applications [1,2,3]. Overall, two main general mechanisms have been described for accomplishing their antimicrobial activity.…”

Section: Introductionmentioning

confidence: 99%

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Unveiling the Multifaceted Mechanisms of Antibacterial Activity of Buforin II and Frenatin 2.3S Peptides from Skin Micro-Organs of the Orinoco Lime Treefrog (Sphaenorhynchus lacteus)

Muñoz-Camargo

Salazar

Barrero-Guevara

et al. 2018

IJMS

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Amphibian skin is a rich source of natural compounds with diverse antimicrobial and immune defense properties. Our previous studies showed that the frog skin secretions obtained by skin micro-organs from various species of Colombian anurans have antimicrobial activities against bacteria and viruses. We purified for the first time two antimicrobial peptides from the skin micro-organs of the Orinoco lime treefrog (Sphaenorhynchus lacteus) that correspond to Buforin II (BF2) and Frenatin 2.3S (F2.3S). Here, we have synthesized the two peptides and tested them against Gram-negative and Gram-positive bacteria, observing an effective bactericidal activity at micromolar concentrations. Evaluation of BF2 and F2.3S membrane destabilization activity on bacterial cell cultures and synthetic lipid bilayers reveals a distinct membrane interaction mechanism. BF2 agglutinates E. coli cells and synthetic vesicles, whereas F2.3S shows a high depolarization and membrane destabilization activities. Interestingly, we found that F2.3S is able to internalize within bacterial cells and can bind nucleic acids, as previously reported for BF2. Moreover, bacterial exposure to both peptides alters the expression profile of genes related to stress and resistance response. Overall, these results show the multifaceted mechanism of action of both antimicrobial peptides that can provide alternative tools in the fight against bacterial resistance.

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Unveiling the Multifaceted Mechanisms of Antibacterial Activity of Buforin II and Frenatin 2.3S Peptides from Skin Micro-Organs of the Orinoco Lime Treefrog (Sphaenorhynchus lacteus)

Muñoz-Camargo

Salazar

Barrero-Guevara

et al. 2018

IJMS

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“…Recently published analysis of the available patent information referring to the therapeutic use of AMPs covering the period from 2003 to 2015 concluded that most of the claimed AMPs were characterized not only as potent antibiotics, but also as effective modulators of inflammation or neutralizers of pathogenic toxins (Kosikowska and Lesner, 2016). The broad range of immunomodulatory activities exerted by AMPs include stimulation of chemotaxis, modulation of immune cell differentiation and initiation of adaptive immunity, together contributing to the bacterial clearance of the host (Figure 4).…”

Section: Mechanism Of Action Of Ampsmentioning

confidence: 99%

“…In spite of large number of AMPs going through clinical development, there is still a considerable discrepancy between the list of AMPs claimed as potent drug candidates in the patents or related scientific articles and the real outcomes of the clinical trials (Kosikowska and Lesner, 2016). Below, some of the technical, regulatory, and commercial challenges to bring AMP-based drugs into the clinical development are highlighted.…”

Section: Challenges To Develop Amps For Clinical Applicationsmentioning

confidence: 99%

Antimicrobial Peptides: An Emerging Category of Therapeutic Agents

Mahlapuu

Håkansson

Ringstad

et al. 2016

Front. Cell. Infect. Microbiol.

1,412

1,316

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Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs.

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“…In general, antimicrobial peptides (AMPs) are getting more and more attention as novel promising therapeutic agents against antibiotic resistant bacteria [113][114][115].…”

Section: J Rifamycinsmentioning

confidence: 99%

Fighting bacterial resistance: approaches, challenges, and opportunities in the search for new antibiotics.Part 1. Antibiotics used in clinical practice: mechanisms of action and the development of bacterial resistance

Zhivich

2017

Microbiology Independent Research Journal (MIR Journal)

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Hundreds of thousands of people are dying every year in the world from infections caused by drug resistant bacteria. Antibiotic resistance is a rapidly increasing problem mostly as a result of the worldwide overuse and misuse of antibiotics for conditions that do not require them. The rapid spread of antibiotic resistance in bacteria makes it necessary to intensify the development of new antibiotics and new methods to combat drug resistant bacteria. The goal of this publication is to review the approaches to finding new antibiotics that are active against drug resistant bacteria. The first part of this review is focused on an analysis of the mechanisms of action of antibiotics that are used in clinical practice as well as the mechanisms of bacterial resistance. The molecular structure and modes of action of these antibiotics are reviewed with examples of detailed mechanisms of drugs interaction with the targets in bacteria. General and specific mechanisms of bacterial resistance to these antibiotics are described. Examples of new antibiotics development active against the drug resistant bacteria are presented.

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Antimicrobial peptides (AMPs) as drug candidates: a patent review (2003–2015)

Cited by 139 publications

References 63 publications

Unveiling the Multifaceted Mechanisms of Antibacterial Activity of Buforin II and Frenatin 2.3S Peptides from Skin Micro-Organs of the Orinoco Lime Treefrog (Sphaenorhynchus lacteus)

Unveiling the Multifaceted Mechanisms of Antibacterial Activity of Buforin II and Frenatin 2.3S Peptides from Skin Micro-Organs of the Orinoco Lime Treefrog (Sphaenorhynchus lacteus)

Antimicrobial Peptides: An Emerging Category of Therapeutic Agents

Fighting bacterial resistance: approaches, challenges, and opportunities in the search for new antibiotics.Part 1. Antibiotics used in clinical practice: mechanisms of action and the development of bacterial resistance

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