Niclosamide as a promising antibiofilm agent

Журина, М. В.; Ганнесен, А. В.; Mart’yanov, S. V.; Teteneva, N. A.; Shtratnikova, Victoria; Плакунов, В. К.

doi:10.1134/s0026261717040154

Cited by 21 publications

(15 citation statements)

References 31 publications

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“…S. aureus 209P (ATCC 6538P, type strain), and S. epidermidis ATCC 14990 (type strain, isolated from nasal mucosa) were stored at room temperature in semisolid lysogeny broth (LB, Dia-M, Moscow, Russia) with 0.5% agar covered with sterile mineral oil. Both of these strains are able to form well-established biofilms which was shown in previous studies [ 13 , 14 , 15 ]. Cultures were prepared in LB and grown overnight with shaking at 150 rpm.…”

Section: Methodssupporting

confidence: 69%

The Impact of Norepinephrine on Mono-Species and Dual-Species Staphylococcal Biofilms

et al. 2021

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The effect of norepinephrine (“NE”) on Gram-negative bacteria is well characterized; however, little is known about the impact of NE on cutaneous Gram-positive skin residents, especially staphylococci. In this study, the impact of NE on monospecies and dual-species biofilms of Staphylococcus epidermidis and S. aureus model strains was investigated for the first time. Biofilms were grown in two different models (on polytetrafluoroethylene (“PTFE”) cubes and glass microfiber filters (“GMFFs”)) and additionally kinetic measurements of bacterial growth was performed. We have shown that NE can affect the biofilm formation of both species with a strong dependence on aerobic or anaerobic culture conditions in different models. It was shown that S. epidermidis suppresses S. aureus growth in dual-species biofilms and that NE can accelerate this process, contributing to the competitive behavior of staphylococci.

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Section: Methodssupporting

confidence: 69%

The Impact of Norepinephrine on Mono-Species and Dual-Species Staphylococcal Biofilms

et al. 2021

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“…Bacterial strains and growth conditions. Micrococcus luteus C01 was isolated from the skin of a healthy volunteer and identified by 16S rRNA sequencing, as described previously [ 30 ]. The bacterium was conserved at room temperature (RT) in glass tubes filled with 5 mL lysogeny broth (LB, Lennox, Dia-M, Moscow, Russia) with the addition of 0.3% agar (BD, USA), and cultures were grown on the surface of semisolid agar and covered with sterile mineral oil.…”

Section: Methodsmentioning

confidence: 99%

Epinephrine affects gene expression levels and has a complex effect on biofilm formation in Micrococcus luteus strain C01 isolated from human skin

Ганнесен

Schelkunov

Geras’kina

et al. 2021

Biofilm

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In this study, the effect of epinephrine on the biofilm formation of Micrococcus luteus C01 isolated from human skin was investigated in depth for the first time. This hormone has a complex effect on biofilms in various systems. In a system with polytetrafluoroethylene (PTFE) cubes, treatment with epinephrine at a physiological concentration of 4.9 × 10 −9 M increased the total amount of 72-h biofilm biomass stained with crystal violet and increased the metabolic activity of biofilms, but at higher and lower concentrations, the treatment had no significant effect. On glass fiber filters, treatment with the hormone decreased the number of colony forming units (CFUs) and changed the aggregation but did not affect the metabolic activity of biofilm cells. In glass bottom plates examined by confocal microscopy, epinephrine notably inhibited the growth of biofilms. RNA-seq analysis and RT–PCR demonstrated reproducible upregulation of genes encoding Fe–S cluster assembly factors and cyanide detoxification sulfurtransferase, whereas genes encoding the co-chaperone GroES, the LysE superfamily of lysine exporters, short-chain alcohol dehydrogenase and the potential c-di-GMP phosphotransferase were downregulated. Our results suggest that epinephrine may stimulate matrix synthesis in M. luteus biofilms, thereby increasing the activity of NAD(H) oxidoreductases. Potential c-di-GMP pathway proteins are essential in these processes.

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“…The broad-spectrum pharmaceutical utility of NIC appears to be related to its protonophoric activity, which results in disruptions of membrane pH gradients that may cause alterations in several signaling pathways [7][8][9][10][11][12][13][14][15][16]. The drug's non-specific mechanism of action is illustrated by its efficacy against both gram-positive and gram-negative bacteria, including Staphylococcus aureus [17][18][19], Pseudomonas aeruginosa [20][21][22], Acinetobacter baumannii [20,23], Mycobacterium tuberculosis [24,25], and various bacterial biofilms [18,19,26], which may enable protection against secondary bacterial pneumonias associated with COVID-19. Furthermore, NIC has been noted to inhibit inflammatory cytokine release in lung tissues in vivo [27], which may provide an important protective effect against cytokine storm and acute respiratory distress syndrome (ARDS), one of the most feared sequela of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Development and evaluation of inhalable composite niclosamide-lysozyme particles: A broad-spectrum, patient-adaptable treatment for coronavirus infections and sequalae

et al. 2021

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Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, administration of the currently available oral formulation results in systemic drug levels that are too low for the inhibition of SARS-CoV-2. We hypothesized that the co-formulation of NIC with an endogenous protein, human lysozyme (hLYS), could enable the direct aerosol delivery of the drug to the respiratory tract as an alternative to oral delivery, thereby effectively treating COVID-19 by targeting the primary site of SARS-CoV-2 acquisition and spread. To test this hypothesis, we engineered and optimized composite particles containing NIC and hLYS suitable for delivery to the upper and lower airways via dry powder inhaler, nebulizer, and nasal spray. The novel formulation demonstrates potent in vitro and in vivo activity against two coronavirus strains, MERS-CoV and SARS-CoV-2, and may offer protection against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage occurring secondary to SARS-CoV-2 infections. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure rapid clinical development and wide-spread utilization.

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Niclosamide as a promising antibiofilm agent

Cited by 21 publications

References 31 publications

The Impact of Norepinephrine on Mono-Species and Dual-Species Staphylococcal Biofilms

The Impact of Norepinephrine on Mono-Species and Dual-Species Staphylococcal Biofilms

Epinephrine affects gene expression levels and has a complex effect on biofilm formation in Micrococcus luteus strain C01 isolated from human skin

Development and evaluation of inhalable composite niclosamide-lysozyme particles: A broad-spectrum, patient-adaptable treatment for coronavirus infections and sequalae

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