Development of novel ultrashort antimicrobial peptide nanoparticles with potent antimicrobial and antibiofilm activities against multidrug-resistant bacteria

Almaaytah, Ammar; Mohammed, Gubran Khalil; Abualhaijaa, Ahmad; Al-Balas, Qosay

doi:10.2147/dddt.s147450

Cited by 81 publications

(65 citation statements)

References 45 publications

(43 reference statements)

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“…Host defense peptides (HDP) are promising antibacterial compounds considered to be promising candidates due to their broad range of activity and multiple mechanism of action [9][10][11] which leads to less resistance developed by the bacteria so HDP are new popular topic for research all over the world [12][13][14]. The broad spectrum of HDP makes them suitable for future medical applications; in this sense, nanotechnology provides promising support for peptide transport and targeted delivery with strongly enhanced biocidal properties and significant reduction of toxicity [15][16][17][18]. Indeed, there are many HDP under clinical developments for treating wide variety of diseases [19].…”

Section: Introductionmentioning

confidence: 99%

Nano-encapsulated HHC10 host defense peptide (HDP) reduces the growth of Escherichia coli via multimodal mechanisms

Sharma

Vaghasiya

Ray

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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The eradication of several pathogenic drug resistant "Superbug" such as Escherichia coli became difficult especially in chronic infections using existing antibiotics due to the emergence of antibiotic resistance. Owing to their unique antibacterial properties, host defense peptides (HDP) have gained significant attention to combat colonization of bacteria. This study aims designing delivery systems for HHC10 peptide to target bacteria inside the cells might be a promising approach by protecting from degradation, controlling the release, enhancing the susceptibility of target microbes and improving bioavailability. Nano-formulated HHC10 was evaluated for its efficacy (CFU assay) and possible mechanism of action (membrane interaction and apoptosis) against E. coli. Dose-dependent inhibition of E. coli growth is observed for nano-encapsulated and bare HHC10 and encapsulated form remain non-toxic to macrophage mouse cells (RAW264.6) up to 20 μM. Mechanistic analyses using transmission electron microscopy and flow cytometry techniques revealed that bactericidal activity of HHC10-NP progresses via a multimodal mechanism of bacterial cell death by cell-membrane lysis on direct interaction with bacteria while through induction of the apoptotic death pathway inside the host cells. These results offer an insight on future strategies for the development and application of antimicrobial peptides as antibacterial alternatives. [Formula: see text] Controlled delivery of HHC10 peptide from PLGA-NP kills bacteria by two different mechanism: (i) direct killing: HHC10 disintegrate the cell membrane of bacteria by electrostatic interactions and (ii) indirect killing: induction of apoptosis in bacteria infect cells.

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Section: Introductionmentioning

confidence: 99%

Nano-encapsulated HHC10 host defense peptide (HDP) reduces the growth of Escherichia coli via multimodal mechanisms

Sharma

Vaghasiya

Ray

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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“…Researchers must solve this problem by developing new compounds. Among new biomedical alternatives, CAMPs are considered candidates with great promise [ 29 – 31 ]. exert various biological functions, like antimicrobial activity, anticancer activity, antihypertensive activity, anti-inflammatory activity, and so forth [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Antimicrobial Peptide Nal-P-113 on Inhibiting Periodontal Pathogens and Improving Periodontal Status

Wang

Cheng

et al. 2018

BioMed Research International

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Periodontal disease consists of chronic gingival inflammation characterized by both degradation of the periodontal connective tissue and alveolar bone loss. Drug therapy is used as an auxiliary treatment method in severe chronic periodontitis, aggressive periodontitis, and periodontitis-associated systemic disease. Nal-P-113, a modified antimicrobial peptide, specifically replaces the histidine residues of P-113 with the bulky amino acid β-naphthylalanine, and our previous studies have verified that this novel peptide is not toxic to the human body within a certain concentration range. The objective of the present study was to evaluate the effect of Nal-P-113 on periodontal pathogens and periodontal status in clinical studies. In a split-mouth clinical trial, the pocket depth and bleeding index values tended to decrease in the experimental group compared with those in the control group. SEM results verified that Nal-P-113 restrained the maturation of plaque. Based on real-time polymerase chain reaction, the levels of Fusobacterium nucleatum, Streptococcus gordonii, Treponema denticola, and Porphyromonas gingivalis in subgingival plaque were decreased when the subjects were given Nal-P-113. Bacterial growth curve analysis and a biofilm susceptibility assay verified that Nal-P-113 at a concentration of 20 μg/mL restrained the growth of S. gordonii, F. nucleatum, and P. gingivalis and biofilm formation. Therefore, Nal-P-113 effectively reduces periodontal pathogens and ameliorates periodontal status.

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“…Several HDPs display potent antimicrobial activity but suffer from severe toxicity and hemolytic activity against normal cells. To overcome this dilemma, many studies focused on advising new methods to limit the cytotoxicity of HDPs either through structural modification or novel formulation technologies [ 23 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

A3, a Scorpion Venom Derived Peptide Analogue with Potent Antimicrobial and Potential Antibiofilm Activity against Clinical Isolates of Multi-Drug Resistant Gram Positive Bacteria

et al. 2018

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Current research in the field of antimicrobials is focused on developing novel antimicrobial agents to counteract the huge dilemma that the human population is mainly facing in regards to the rise of bacterial resistance and biofilm infections. Host defense peptides (HDPs) are a promising group of molecules for antimicrobial development as they display several attractive features suitable for antimicrobial activity, including their broad spectrum of activity and potency against bacteria. AamAP1 is a novel HDP that belongs to the venom of the North African scorpion Androctonus amoeruxi. In vitro antimicrobial assays revealed that the peptide displays moderate activity against Gram-positive and Gram-negative bacteria. Additionally, the peptide proved to be highly hemolytic and displayed significantly high toxicity against mammalian cells. In our study, a novel synthetic peptide analogue named A3 was synthetically modified from AamAP1 in order to enhance its activity and toxicity profile. The design strategy depended on modifying the amino acid sequence of AamAP1 in order to alter its net positive charge, percentage helicity and modify other parameters that are involved theoretically in HDPs activity. Accordingly, A3 was evaluated for its in vitro antimicrobial and anti-biofilm activity individually and in combination with four different types of conventional antibiotics against clinical isolates of multi-drug resistant (MDR) Gram-positive bacteria. A3 was also evaluated for its cytotoxicity against mammalian cells. A3 managed to selectively inhibit the growth of a wide range of resistant strains of Gram-positive bacteria. Our results also showed that combining A3 with conventional antibiotics caused a synergistic antimicrobial behavior that resulted in decreasing the MIC value for A3 peptide as low as 0.125 µM. At the concentrations needed to inhibit bacterial growth, A3 displayed minimal mammalian cell toxicity. In conclusion, A3 exhibits enhanced activity and selectivity when compared with the parent natural scorpion venom peptide. The combination of A3 with conventional antibiotics could provide researchers in the antimicrobial drug development field with a potential alternative for conventional antibiotics against MDR bacteria.

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Development of novel ultrashort antimicrobial peptide nanoparticles with potent antimicrobial and antibiofilm activities against multidrug-resistant bacteria

Cited by 81 publications

References 45 publications

Nano-encapsulated HHC10 host defense peptide (HDP) reduces the growth of Escherichia coli via multimodal mechanisms

Nano-encapsulated HHC10 host defense peptide (HDP) reduces the growth of Escherichia coli via multimodal mechanisms

The Effects of Antimicrobial Peptide Nal-P-113 on Inhibiting Periodontal Pathogens and Improving Periodontal Status

A3, a Scorpion Venom Derived Peptide Analogue with Potent Antimicrobial and Potential Antibiofilm Activity against Clinical Isolates of Multi-Drug Resistant Gram Positive Bacteria

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