Antimicrobial peptides under clinical investigation

Koo, Hye Been; Seo, Jiwon

doi:10.1002/pep2.24122

Cited by 299 publications

(267 citation statements)

References 111 publications

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“…It was developed by Zengen, Abiogen Pharma and Lee's pharmaceuticals (Duncan and O'Neil, 2013) 5 . In addition, there are many cases of peptides with promising properties currently being evaluated pre-clinically (Koo and Seo, 2019). Other pre-clinical examples are described in the review by Duncan and O'Neill (Duncan and O'Neil, 2013) and in the database DRAMP 2.0 (Kang et al, 2019).…”

Section: Potential Applicationsmentioning

confidence: 99%

Antifungal Peptides as Therapeutic Agents

Ullivarri

Arbulu

García-Gutiérrez

et al. 2020

Front. Cell. Infect. Microbiol.

174

132

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Fungi have been used since ancient times in food and beverage-making processes and, more recently, have been harnessed for the production of antibiotics and in processes of relevance to the bioeconomy. Moreover, they are starting to gain attention as a key component of the human microbiome. However, fungi are also responsible for human infections. The incidence of community-acquired and nosocomial fungal infections has increased considerably in recent decades. Antibiotic resistance development, the increasing number of immunodeficiency-and/or immunosuppression-related diseases and limited therapeutic options available are triggering the search for novel alternatives. These new antifungals should be less toxic for the host, with targeted or broader antimicrobial spectra (for diseases of known and unknown etiology, respectively) and modes of actions that limit the potential for the emergence of resistance among pathogenic fungi. Given these criteria, antimicrobial peptides with antifungal properties, i.e., antifungal peptides (AFPs), have emerged as powerful candidates due to their efficacy and high selectivity. In this review, we provide an overview of the bioactivity and classification of AFPs (natural and synthetic) as well as their mode of action and advantages over current antifungal drugs. Additionally, natural, heterologous and synthetic production of AFPs with a view to greater levels of exploitation is discussed. Finally, we evaluate the current and potential applications of these peptides, along with the future challenges relating to antifungal treatments.

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Section: Potential Applicationsmentioning

confidence: 99%

Antifungal Peptides as Therapeutic Agents

Ullivarri

Arbulu

García-Gutiérrez

et al. 2020

Front. Cell. Infect. Microbiol.

174

132

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“…Pexiganan is a synthetic AMP analog of magainin, that exhibits a broad-spectrum of action and acts by disrupting the bacterial cell membrane through toroidal-type pore formation [16]. Pexiganan was originally developed by Magainin Pharmaceuticals for the treatment of infected diabetic foot ulcers and was the only AMP that reached phase III clinical trials aiming at evaluating its wound healing properties towards DFI [17]. Despite the fact that pexiganan cream formulation evaluated in those trials was not able to demonstrate a clear advantage over conventional oral antibiotics [18,19] or a topical placebo control [19][20][21], it is still one of the best-studied AMPs for therapeutic purposes [16].…”

Section: Introductionmentioning

confidence: 99%

Pexiganan in Combination with Nisin to Control Polymicrobial Diabetic Foot Infections

et al. 2020

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Diabetic foot ulcers (DFUs) are major complications of Diabetes mellitus being responsible for significant morbidity and mortality. DFUs frequently become chronically infected by a complex community of bacteria, including multidrug-resistant and biofilm-producing strains of Staphylococcus aureus and Pseudomonas aeruginosa. Diabetic foot infections (DFI) are often recalcitrant to conventional antibiotics and alternative treatment strategies are urgently needed. Antimicrobial Peptides (AMPs), such as pexiganan and nisin, have been increasingly investigated and reported as effective antimicrobial agents. Here, we evaluated the antibacterial potential of pexiganan and nisin used in combination (dual-AMP) to control the growth of planktonic and biofilm co-cultures of S. aureus and P. aeruginosa clinical strains, co-isolated from a DFU. A DFU collagen three-dimensional (3D) model was used to evaluate the distribution and efficacy of AMPs locally delivered into the model. The concentration of pexiganan required to inhibit and eradicate both planktonic and biofilm-based bacterial cells was substantially reduced when used in combination with nisin. Moreover, incorporation of both AMPs in a guar gum delivery system (dual-AMP biogel) did not affect the dual-AMP antimicrobial activity. Importantly, the application of the dual-AMP biogel resulted in the eradication of the S. aureus strain from the model. In conclusion, data suggest that the local application of the dual-AMPs biogel constitutes a potential complementary therapy for the treatment of infected DFU.

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“…Therefore, AMPs represent promising lead compounds in the fight against multidrug-resistant bacteria [Mookherjee 2020, Koo 2019, Fox 2013, which constitute a dramatically increasing worldwide threat [Ventola 2015], and several peptides are undergoing clinical trials [Koo 2019].…”

Section: Introductionmentioning

confidence: 99%

Inoculum effect of antimicrobial peptides

Loffredo

Savini

Bobone

et al. 2020

Preprint

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The activity of many antibiotics depends on the initial density of cells used in bacteria growth inhibition assays. This phenomenon, termed the inoculum effect, can have important consequences for the therapeutic efficacy of the drugs, since bacterial loads vary by several orders of magnitude in clinically relevant infections. Antimicrobial peptides are a promising class of molecules to fight drug-resistant bacteria, since they act mainly by perturbing the cell membranes rather than by inhibiting intracellular targets. Here we report the first systematic characterization of the inoculum effect for this class of antibacterial compounds. Thirteen peptides (including all-D enantiomers) and peptidomimetics were analyzed by measuring minimum inhibitory concentration values, covering more than 7 orders of magnitude in inoculated cell density. In all cases, we observed a significant inoculum effect for cell densities above 5 x 104 cells/mL, while the active concentrations remained constant (within the micromolar range) for lower densities. In the case of membrane-active peptides, these data can be rationalized by considering a simple model, taking into account peptide-cell association and hypothesizing that a threshold number of cell-bound peptide molecules is required in order to cause a killing effect. The observed effects question the clinical utility of activity and selectivity determinations performed at a fixed, standardized cell density. A routine evaluation of the inoculum dependence of the activity of antimicrobial peptides and peptidomimetics should be considered.

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Antimicrobial peptides under clinical investigation

Cited by 299 publications

References 111 publications

Antifungal Peptides as Therapeutic Agents

Antifungal Peptides as Therapeutic Agents

Pexiganan in Combination with Nisin to Control Polymicrobial Diabetic Foot Infections

Inoculum effect of antimicrobial peptides

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