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Antibacterial compositions

A composition and compound technology, applied in the direction of antibacterial drugs, non-active ingredients of polymer compounds, drug delivery, etc., can solve the problems of inconsistent toxic effects and direct toxic effects of niclosamide, etc.

Inactive Publication Date: 2019-03-15
VICTORIA LINK LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the authors did not consider a direct toxic effect of niclosamide, and their data are inconsistent with any direct toxic effect of niclosamide against Pseudomonas aeruginosa

Method used

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  • Antibacterial compositions
  • Antibacterial compositions
  • Antibacterial compositions

Examples

Experimental program
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Embodiment 1

[0381] Example 1: Antibiotic Combination / Growth Assay

[0382] This action applies to Figure 1-Figure 52The experiments described in . Inoculate the desired bacterial strain in 3 mL of LB and incubate at 30 °C for 16 h, shaking at 250 rpm. A 500 μL aliquot of each overnight culture was used to inoculate 20 ml of LB in a 50 ml bioreactor tube and incubate for 2 hours at 30°C, 250 rpm, or as otherwise indicated in the figure caption. 40 μL of each culture was then added to a substance containing salicylamide (such as niclosamide, oxyclozanide, nitzoxanel, or chlorsentyl) and a substance that increases the permeability of the bacterial cell membrane (such as polymyxin B , polymyxin E (colistin), gramicidin) in a multiplex assay (quadruplicate) in 384-well plate format. Each well of a 384-well plate contained 40 [mu]L of LB corrected to double the final expected concentration of the desired drug combination to allow for a 1 :2 dilution of the bacterial culture. OD600 was meas...

Embodiment 2

[0389] Example 2: In vivo real-time measurement of redox potential in bacteria

[0390] Generation of redox screening strains of E. coli

[0391] Redox screening strains were generated by the in-frame deletion method using the PCR amplification destruction cassette by the Red recombinase method (Datsenko & Warner (2000) Proc Natl Acad Sci US A97, 6640-6645). E. coli strain 7KO was derived from E. coli strain W3110 by deleting the native nfsA, nfsB, azoR, nemA, yieF, ycaK and mdaB genes as previously described by Copp et al. (Copp et al. (2014) Protein Eng. Des. Sel. 27 , 399-403). E. coli strain 7KOΔtolC was derived from 7KO by deletion of the native tolC gene. The pFPX25-roGFP2 vector (van der Heijden et al. (2015) Proc Natl Acad Sci USA 112, 560-565) was cloned into E. coli strains 7KO and 7KOΔtolC to generate 7KO:roGFP and 7KOΔtolC:roGFP, respectively.

[0392] In vivo real-time measurement of redox potential in bacteria

[0393] In vivo analysis of the redox potential ...

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Abstract

The present invention provides compositions, including pharmaceutical compositions, comprising a salicylamide compound and an agent that increases the permeability of a bacterial cell membrane for usein treating or preventing bacterial infections.

Description

technical field [0001] The present invention generally relates to the combination of a salicylamide compound effective in preventing or treating bacterial infection and a substance that increases the permeability of bacterial cell membrane and the composition thereof. Background technique [0002] It is generally expected that the rise of multidrug-resistant bacteria will be the biggest health problem facing mankind in the 21st century (Boucher et al. (2009) Clinical Infectious Diseases 48(1): 1-12; Piddock (2012) Lancet InfectDis.12(3): 249-53). Clinicians are already routinely confronted with cases of antibiotic resistance, and infections that were previously simple to treat have become more difficult and, in some cases, untreatable. Almost all classes of antibiotics were discovered before 1970, and no new major classes of antibiotics have been developed in the past 30 years. Much of the recent progress towards new antibiotic therapies has been within antibiotic classes ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/165A61K47/42A61P31/04
CPCA61K31/609A61K38/12A61K31/426A61K38/00A61P31/04Y02A50/30A61K2300/00A61K9/0019A61K31/166
Inventor D·F·阿克利J·N·科帕
Owner VICTORIA LINK LTD
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