Synthetic Antibacterial Peptide Exhibits Synergy with Oxacillin against MRSA

Lainson, John C.; Daly, Seth M.; Triplett, Kathleen D.; Johnston, Stephen Albert; Hall, Pamela R.; Diehnelt, Chris W.

doi:10.1021/acsmedchemlett.7b00200

Cited by 22 publications

(19 citation statements)

References 27 publications

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“…These features of peptidomimetics enable design of compounds with fine-tuned physicochemical properties that confer enhanced antibacterial activity as well as an improved pharmacological profile (Méndez-Samperio, 2014). Moreover, certain peptidomimetics have proved capable of potentiating traditional antibiotics (Renau et al, 2002; Goldberg et al, 2013; Jammal et al, 2015; Lainson et al, 2017), suggesting a possible role in combination therapy. Despite displaying several features that are superior to those of peptides, their therapeutic potential relies on technological advances to enable reduced production cost, improved bioavailability, and minimized toxicity toward host cells (Molchanova et al, 2017a).…”

Section: Introductionmentioning

confidence: 99%

Repurposing Azithromycin and Rifampicin Against Gram-Negative Pathogens by Combination With Peptidomimetics

Baker

Jana

Hansen

et al. 2019

Front. Cell. Infect. Microbiol.

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Synthetic peptidomimetics may be designed to mimic functions of antimicrobial peptides, including potentiation of antibiotics, yet possessing improved pharmacological properties. Pairwise screening of 42 synthetic peptidomimetics combined with the antibiotics azithromycin and rifampicin in multidrug-resistant (MDR) Escherichia coli ST131 and Klebsiella pneumoniae ST258 led to identification of two subclasses of α-peptide/β-peptoid hybrids that display synergy with azithromycin and rifampicin (fractional inhibitory concentration indexes of 0.03–0.38). Further screening of the best three peptidomimetics in combination with a panel of 21 additional antibiotics led to identification of peptidomimetics that potentiated ticarcillin/clavulanate and erythromycin against E. coli , and clindamycin against K. pneumoniae . The study of six peptidomimetics was extended to Pseudomonas aeruginosa , confirming synergy with antibiotics for five of them. The most promising compound, H-(Lys-βNPhe) 8 -NH 2 , exerted only a minor effect on the viability of mammalian cells (EC 50 ≥ 124–210 μM), and thus exhibited the highest selectivity toward bacteria. This compound also synergized with rifampicin and azithromycin at sub-micromolar concentrations (0.25–0.5 μM), thereby inducing susceptibility to these antibiotics at clinically relevant concentrations in clinical MDR isolates. This peptidomimetic lead and its analogs constitute promising candidates for efficient repurposing of rifampicin and azithromycin against Gram-negative pathogens.

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Section: Introductionmentioning

confidence: 99%

Repurposing Azithromycin and Rifampicin Against Gram-Negative Pathogens by Combination With Peptidomimetics

Baker

Jana

Hansen

et al. 2019

Front. Cell. Infect. Microbiol.

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“…Increased anti-staphylococcal activity is known with combined administration of the peptide ASU014 with oxacillin against Staphylococcus aureus. The expressed efficacy was caused by their joint use in comparison with individual drugs against the polyresistant pathogen (Lainson et al, 2017). The ability of PMBN nanopeptide to synergise with antimicrobials in the presence of efflux inhibitors (efflux pump inhibitors) has been established.…”

Section: Discussionmentioning

confidence: 99%

Synergistic activity of filtrates of Lactobacillus rhamnosus and Saccharomyces boulardii and antibacterial preparations against Corynebacterium spp.

Isayenko

2019

Regul. Mech. Biosyst.

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We present the results of the first study of the combined influence of the biologically active substances Lactobacillus rhamnosus GG ATCC 53103 and Saccharomyces boulardii, obtained by the author’s method, and antibacterial agents on Corynebacterium spp. The first area of research was the study of increasing the sensitivity of toxigenic microorganisms to antimicrobial drugs due to the consecutive effects of the structural components and metabolites of L. rhamnosus GG and S. boulardii and antibacterial drugs on Corynebacterium spp. tox+. The greatest increase in the sensitivity of test-cultures of corynebacteria to penicillin (by 19.4 mm), imipenem (by 15.0 mm), vancomycin (by 12.0 mm), gentamicin (by 11.0 mm), ciprofloxacin (by 9.8 mm), erythromycin (by 9.6 mm), cefotaxime (by 9.5 mm) occurred due to the products of lactobacteria and a combination of metabolites of lactobacteria and saccharomycetes. The second area of research was the study of the synergic activity of substances L. rhamnosus GG and S. boulardii and traditional antibacterial drugs manifested by their simultaneous effect on Corynebacterium spp. Maximum potentiation of azithromycin (by 4.6 mm), erythromycin (by 4.5 mm), cefotaxime (by 2.2 mm), ceftriaxone (by 1.6 mm) and ampicillin (by 1.0 mm) relative to corynebacteria was also observed under the influence of lactobacteria metabolites and a combination of lactobacteria and saccharomycetes metabolites. Different degrees of manifestation of the combined action of biologically active substances L. rhamnosus GG and S. boulardii with antibiotics were determined, which depended on the selected combinations, the method of influence on the microorganism, the individual sensitivity of the test-cultures, the activity of the test filtrates and the initial concentration of the producers used to obtain the products of vital activity of lactobacteria and saccharomyces. The presented complexes of structural components and metabolites of L. rhamnosus GG and S. boulardii, obtained without the use of traditional nutrient media, by increasing the bioavailability of pathogenic pathogens can reduce the required concentration of the antibiotic, continuing their use, and suspend the likelihood of pathogens developing resistance to microorganisms. This makes them promising candidates both for the development of "accompaniment-preparations" for antibiotics for the additional therapy of infectious diseases of different etiology, and for the creation of a new direction of antimicrobial agents with multifunctional capabilities. Synergistic activity of filtrates L. rhamnosus GG and S. boulardii and antibacterial preparations against Corynebacterium spp.

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“…2) from aldehydes and alkynes using choline chloride (ChCl): urea as a biorenewable deep eutectic solvent (DES). DES are an environmentally benign alternative to hazardous (Majewsky et al 2014) 2 Sulfisoxazole Antibacterial (Genc et al 2008) 3 Acetyl sulfisoxazole Antibacterial (Cronin et al 2002) 4 Cycloserine Antitubercular, Antileprotic (Desjardins et al 2016) 5 Acivicin Antitumour, Antileishmania (Conti et al 2003) 6 Broxaterol Bronchodilatory agent (Giustina et al 1995) 7 Oxacillin Antibacterial (Lainson et al 2017) (Zhao et al 2017a) 10 Zonisamide Anticonvulsant (Buoli et al 2017), Antiobesity (Shin et al 2014) 11 Risperidone Antpsychotic (Schoretsanitis et al 2017) 12 Valdecoxib COX-2 inhibitor (Bartzatt 2014) 13 Danazol Androgenic (McKinney et al 2013) (organic) solvents that can be recycled (Pérez and Ramón 2015). Jadhav et al synthesized highly pure 3,5-disubstituted isoxazoles (Route d, Fig.…”

Section: Synthetic Methodsmentioning

confidence: 99%

The synthetic and therapeutic expedition of isoxazole and its analogs

2018

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Isoxazole, constituting an important family of five-membered heterocycles with one oxygen atom and one nitrogen atom at adjacent positions is of immense importance because of its wide spectrum of biological activities and therapeutic potential. It is, therefore, of prime importance that the development of new synthetic strategies and designing of new isoxazole derivatives should be based on the most recent knowledge emerging from the latest research. This review is an endeavor to highlight the progress in the chemistry and biological activity of isoxazole derivatives which could provide a low-height flying bird's eye view of isoxazole derivatives to the medicinal chemists for the development of clinically viable drugs using this information.

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Synthetic Antibacterial Peptide Exhibits Synergy with Oxacillin against MRSA

Cited by 22 publications

References 27 publications

Repurposing Azithromycin and Rifampicin Against Gram-Negative Pathogens by Combination With Peptidomimetics

Repurposing Azithromycin and Rifampicin Against Gram-Negative Pathogens by Combination With Peptidomimetics

Synergistic activity of filtrates of Lactobacillus rhamnosus and Saccharomyces boulardii and antibacterial preparations against Corynebacterium spp.

The synthetic and therapeutic expedition of isoxazole and its analogs

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