Potent Activity of Hybrid Arthropod Antimicrobial Peptides Linked by Glycine Spacers

Arthropod antimicrobial peptides (AMPs) offer a promising source of new leads to address the declining number of novel antibiotics and the increasing prevalence of multidrug-resistant bacterial pathogens. AMPs with potent activity against Gram-negative bacteria and distinct modes of action have been identified in insects and scorpions, allowing the discovery of AMP combinations with additive and/or synergistic effects. Here, we tested the synergistic activity of two AMPs, from the dung beetle Copris tripartitus (CopA3) and the scorpion Heterometrus petersii (Hp1090), against two strains of Escherichia coli. We also tested the antibacterial activity of two hybrid peptides generated by joining CopA3 and Hp1090 with linkers comprising two (InSco2) or six (InSco6) glycine residues. We found that CopA3 and Hp1090 acted synergistically against both bacterial strains, and the hybrid peptide InSco2 showed more potent bactericidal activity than the parental AMPs or InSco6. Molecular dynamics simulations revealed that the short linker stabilizes an N-terminal 310-helix in the hybrid peptide InSco2. This secondary structure forms from a coil region that interacts with phosphatidylethanolamine in the membrane bilayer model. The highest concentration of the hybrid peptides used in this study was associated with stronger hemolytic activity than equivalent concentrations of the parental AMPs. As observed for CopA3, the increasing concentration of InSco2 was also cytotoxic to BHK-21 cells. We conclude that AMP hybrids linked by glycine spacers display potent antibacterial activity and that the cytotoxic activity can be modulated by adjusting the nature of the linker peptide, thus offering a strategy to produce hybrid peptides as safe replacements or adjuncts for conventional antibiotic therapy.

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Antimicrobial Peptides Display Strong Synergy with Vancomycin Against Vancomycin-Resistant E. faecium, S. aureus, and Wild-Type E. coli

International Journal of Molecular Sciences ◽

10.3390/ijms21134578 ◽

2020 ◽

Vol 21 (13) ◽

pp. 4578 ◽

Cited By ~ 3

Author(s):

Chih-Lung Wu ◽

Ju-Yun Hsueh ◽

Bak-Sau Yip ◽

Ya-Han Chih ◽

Kuang-Li Peng ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Synergistic Effects ◽

Synergistic Activity ◽

Wild Type ◽

Bacterial Strains ◽

Antibiotic Resistant ◽

Minimal Inhibitory Concentrations ◽

E Coli ◽

Large Size ◽

Vancomycin Resistant

There is an urgent and imminent need to develop new antimicrobials to fight against antibiotic-resistant bacterial and fungal strains. In this study, a checkerboard method was used to evaluate the synergistic effects of the antimicrobial peptide P-113 and its bulky non-nature amino acid substituted derivatives with vancomycin against vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, and wild-type Escherichia coli. Boron-dipyrro-methene (BODIPY) labeled vancomycin was used to characterize the interactions between the peptides, vancomycin, and bacterial strains. Moreover, neutralization of antibiotic-induced releasing of lipopolysaccharide (LPS) from E. coli by the peptides was obtained. Among these peptides, Bip-P-113 demonstrated the best minimal inhibitory concentrations (MICs), antibiotics synergism, bacterial membrane permeabilization, and supernatant LPS neutralizing activities against the bacteria studied. These results could help in developing antimicrobial peptides that have synergistic activity with large size glycopeptides such as vancomycin in therapeutic applications.

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Chemical Composition and Antibacterial Activity of Berries Essential Oil of Algerian Juniperus thurifera (Var. aurasiaca)

Pharmaceutical Sciences ◽

10.15171/ps.2018.35 ◽

2018 ◽

Vol 24 (3) ◽

pp. 240-245

Author(s):

Lamia Boudjedjou ◽

Messaoud Ramdani ◽

Azzeddine Zeraib ◽

Tarek Benmeddour ◽

Azzedine Fercha

Keyword(s):

Antibacterial Activity ◽

Chemical Composition ◽

Essential Oil ◽

Synergistic Effects ◽

Diffusion Method ◽

Bacterial Strains ◽

Juniperus Thurifera ◽

E Coli ◽

Conventional Antibiotics ◽

Promising Source

Background: Over the past decade, most antibiotic research programs have focused on finding new compounds with antimicrobial activity. This study aims to investigate the chemical composition and antibacterial activity of the essential oil (EO) extracted from ripe berries of Algerian Juniperus thurifera var. aurasiaca. Methods: The chemical composition of J. thurifera EO extracted by hydrodistillation was analyzed by using the GC-MS technique. Antibacterial activity of EO alone and in combination with three conventional antibiotics was assessed by using disc diffusion method against four bacterial strains. Results: Thirty-five components were identified, representing ~87 % of the oil. The main components were m-mentha-6,8-diene (15.43 %), β-pinene (10.59 %), elemol (8.31 %) and terpinene-4-ol (7.44 %). The essential oil showed strong antibacterial activity against S. aureus and E. coli, but no activity against P. aeruginosa and B. subtilis. Synergistic effects were observed because of the combined application of EO with gentamicin against all strains tested, and with amoxicillin against B. subtilis. Furthermore, the combination of EO/cefazolin demonstrated an additive effect against B. subtilis. In contrast, the combination of EO with amoxicillin and céfazoline revealed antagonistic effects against S. aureus, E. coli, and P. aeruginosa. Conclusion: This is the first report on the chemical composition and antibacterial activity of Algerian juniper berries’ essential oil. The results indicate that the studied EO may be a promising source of antibacterial compounds that could be useful for pharmaceutical applications especially in combination with conventional antibiotics.

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Botanicals and phytochemicals from the bark of Hypericum roeperianum (Hypericaceae) had strong antibacterial activity and showed synergistic effects with antibiotics against multidrug-resistant bacteria expressing active efflux pumps.

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.114257 ◽

2021 ◽

pp. 114257

Author(s):

Olive Monique F. Demgne ◽

Francois Damen ◽

Aimé G. Fankam ◽

Michel-Gael F. Guefack ◽

Brice E.N. Wamba ◽

...

Keyword(s):

Antibacterial Activity ◽

Synergistic Effects ◽

Efflux Pumps ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Multidrug Resistant Bacteria ◽

Active Efflux

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Production of putrescine-capped stable silver nanoparticle: its characterization and antibacterial activity against multidrug-resistant bacterial strains

Applied Nanoscience ◽

10.1007/s13204-016-0528-9 ◽

2016 ◽

Vol 6 (8) ◽

pp. 1137-1147 ◽

Cited By ~ 2

Author(s):

Saswati Saha ◽

Bhaskar Gupta ◽

Kamala Gupta ◽

Mahua Ghosh Chaudhuri

Keyword(s):

Antibacterial Activity ◽

Silver Nanoparticle ◽

Multidrug Resistant ◽

Bacterial Strains

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Formulation and Evaluation of Antibacterial Creams and Gels Containing Metal Ions for Topical Application

Journal of Pharmaceutics ◽

10.1155/2016/5754349 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Mei X. Chen ◽

Kenneth S. Alexander ◽

Gabriella Baki

Keyword(s):

Antibacterial Activity ◽

Metal Ions ◽

Copper Sulfate ◽

Zinc Sulfate ◽

Antimicrobial Properties ◽

Multidrug Resistant ◽

Synergistic Activity ◽

Minimum Effective Concentration ◽

Organoleptic Characteristics

Background. Skin infections occur commonly and often present therapeutic challenges to practitioners due to the growing concerns regarding multidrug-resistant bacterial, viral, and fungal strains. The antimicrobial properties of zinc sulfate and copper sulfate are well known and have been investigated for many years. However, the synergistic activity between these two metal ions as antimicrobial ingredients has not been evaluated in topical formulations. Objective. The aims of the present study were to (1) formulate topical creams and gels containing zinc and copper alone or in combination and (2) evaluate the in vitro antibacterial activity of these metal ions in the formulations. Method. Formulation of the gels and creams was followed by evaluating their organoleptic characteristics, physicochemical properties, and in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus. Results. Zinc sulfate and copper sulfate had a strong synergistic antibacterial activity in the creams and gels. The minimum effective concentration was found to be 3 w/w% for both active ingredients against the two tested microorganisms. Conclusions. This study evaluated and confirmed the synergistic in vitro antibacterial effect of copper sulfate and zinc sulfate in a cream and two gels.

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Production of a New Thiopeptide Antibiotic, TP-1161, by a Marine Nocardiopsis Species

Applied and Environmental Microbiology ◽

10.1128/aem.00741-10 ◽

2010 ◽

Vol 76 (15) ◽

pp. 4969-4976 ◽

Cited By ~ 104

Author(s):

Kerstin Engelhardt ◽

Kristin F. Degnes ◽

Michael Kemmler ◽

Harald Bredholt ◽

Espen FjÃ¯Â¿Â½rvik ◽

...

Keyword(s):

Antibacterial Activity ◽

Molecular Taxonomy ◽

Multidrug Resistant ◽

Peptide Antibiotic ◽

Indicator Organisms ◽

Bacterial Strains ◽

Pcr Screening ◽

Vancomycin Resistant ◽

Antibacterial And Antifungal

ABSTRACT Twenty-seven marine sediment- and sponge-derived actinomycetes with a preference for or dependence on seawater for growth were classified at the genus level using molecular taxonomy. Their potential to produce bioactive secondary metabolites was analyzed by PCR screening for genes involved in polyketide and nonribosomal peptide antibiotic synthesis. Using microwell cultures, conditions for the production of antibacterial and antifungal compounds were identified for 15 of the 27 isolates subjected to this screening. Nine of the 15 active extracts were also active against multiresistant Gram-positive bacterial and/or fungal indicator organisms, including vancomycin-resistant Enterococcus faecium and multidrug-resistant Candida albicans. Activity-guided fractionation of fermentation extracts of isolate TFS65-07, showing strong antibacterial activity and classified as a Nocardiopsis species, allowed the identification and purification of the active compound. Structure elucidation revealed this compound to be a new thiopeptide antibiotic with a rare aminoacetone moiety. The in vitro antibacterial activity of this thiopeptide, designated TP-1161, against a panel of bacterial strains was determined.

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Chemical Composition, Antioxidant and Antibacterial Activity of Bunium persicum, Eucalyptus globulus, and Rose Water on Multidrug-Resistant Listeria Species

Journal of Evidence-Based Integrative Medicine ◽

10.1177/2515690x17751314 ◽

2018 ◽

Vol 23 ◽

pp. 2515690X1775131 ◽

Cited By ~ 7

Author(s):

Farhad Sharafati Chaleshtori ◽

Mohamad Saholi ◽

Reza Sharafati Chaleshtori

Keyword(s):

Antimicrobial Activity ◽

Antibacterial Activity ◽

Essential Oil ◽

Essential Oils ◽

Eucalyptus Globulus ◽

Multidrug Resistant ◽

Bacterial Strains ◽

Antioxidant Power ◽

Listeria Species ◽

Bunium Persicum

This research was aimed at investigating the antioxidant and antibacterial activity of Bunium persicum, Eucalyptus globulus, and rose water on multidrug-resistant Listeria species. The antibiotic resistance of Listeria spp obtained from seafood samples were determined by the Kirby-Bauer method. The antioxidant and antibacterial activity of the essential oils and extracts were evaluated using ferric reducing antioxidant power and microdilution methods, respectively. A total 2 samples (1.88%) were positive for Listeria spp. L monocytogenes was found to be resistant to ampicillin, amoxicillin/clavulanic acid, penicillin, vancomycin, and kanamycin. B persicum essential oil showed the greatest antioxidant activity (248.56 ± 1.09 µM Fe2+/g). The E globulus essential oil showed consistently strong antimicrobial activity against L monocytogenes and L grayi, while rose water showed no antimicrobial activity against any of the tested bacterial strains. The results showed that after adding the B persicum and E globulus essential oils to bacteria, the cell components’ release increased significantly.

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Phytochemical Screening, Antibacterial and Synergistic activity of Dittrichia Viscosa Extracts against Multi-Resistant Pathogenic Bacteria

Pharmaceutics and Pharmacology Research ◽

10.31579/2693-7247/005 ◽

2019 ◽

Vol 2 (1) ◽

pp. 01-06

Author(s):

Rhazi Fouzia

Keyword(s):

Antibacterial Activity ◽

Pathogenic Bacteria ◽

Antibacterial Effect ◽

Synergistic Activity ◽

Phytochemical Screening ◽

Bacterial Strains ◽

Dittrichia Viscosa ◽

Study Results ◽

Ethanolic Extracts

Study contextual: Faced with the global problem of antimicrobial resistance, and the use of traditional medicine for the research of antibacterial biomolecules. Aim: our work focused on the valorization of a medicinal plant Dittrichia viscosa which has many therapeutic and culinary virtues worldwide. Methods: To do this, a phytochemical screening of the leafy stems of the plant is carried out according to a set of physicochemical reactions, as well as an in vitro evaluation of the antibacterial activity, of the aqueous and ethanolic extracts against multi-resistant bacterial strains, by microdilution technique on microplates. An evaluation of the synergistic interaction between extracts and weakened antibiotics against pathogenic bacteria was also highlighted in this study. Results: The tests revealed the richness of Dittrichia viscosa species by tannins, flavonoids, saponosides, sterols and triterpenes. As for the antibacterial effect, the MICs range from 0.858±0.29 to 66.66 ± 0.00 mg / ml and the MBCs from 4.300 ± 1.01 to 11.610 ± 2.31 mg / ml is an interesting antibacterial activity. Regarding the combination of extracts with antibiotics tested, it revealed a synergistic action inducing an amplification of the antibacterial power of Penicillin, Imipenem and Erythromycin with a rate that reaches 471%. Conclusion: The results of this study show that the aqueous and ethanolic extracts of Dittrichia viscosa have interesting and promising antibacterial activity in the pharmaceutical, food and cosmetic industries.

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Cyathea gigantea (Cyatheaceae) as an antimicrobial agent against multidrug resistant organisms

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2696-0 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Kathakali Nath ◽

Anupam Das Talukdar ◽

Mrinal Kanti Bhattacharya ◽

Deepshikha Bhowmik ◽

Shiela Chetri ◽

...

Keyword(s):

Antibacterial Activity ◽

Antibacterial Property ◽

Treatment Options ◽

Multidrug Resistant ◽

Diffusion Method ◽

Synergistic Activity ◽

Gram Positive ◽

Traditional Use ◽

Gram Negative ◽

Multidrug Resistant Organisms

Abstract Background Rapid emergence of multidrug resistant (MDR) organisms in hospital and community settings often result into treatment failure, thus leading the clinicians with fewer treatment options. Cyathea gigantea, an ethnomedicinally important fern used in cuts and wound infections. So, if this medicinal plant is used in treating the MDR infections then it might bring certain relief in future treatment options. Methods Antibacterial activity of C. gigantea against MDR bacteria was assed using well diffusion and broth microdilution methods to determine the diameters of growth inhibition zones, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Synergistic activity was also determined with the conventional antibiotics by disc diffusion method followed by FIC index of each of the tested antibiotic was calculated. The active extract was then subjected to fractionation by column chromatography and antibacterial activity was done with each of the collected fractions. Results Crude extract of C. gigantea was found to be active against all the tested organisms. The MIC was 200 μg/ml against Gram-positive i.e., Staphylococcus aureus ATCC 25923 and 400 μg/ml against Gram-negative i.e., Escherichia coli ATCC 25922 and Pseudomonas aeruginosa PAO1, while the MBC was 400 μg/ml in case of Gram-positive and 800 μg/ml for Gram-negative. The synergistic activity revealed that the plant extract increased the antibacterial property of the studied antibiotics and the FIC index showed that significant synergistic activity was shown by ciprofloxacin followed by tetracycline, ampicillin and oxacillin. Antibacterial activity with the fractionated extract showed that the FR II, FR III and FR IV were active against both Gram-positive and Gram-negative bacteria, whereas FR I, FR V and FR VI did not show antibacterial property against any of the tested bacteria. Conclusions Extracts of C. gigantea was found active against both selected Gram-positive and Gram-negative organisms and thus offers the scientific basis for the traditional use of the fern. The present study also provides the basis for future study to validate the possible use against multidrug resistant organisms.

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