Cellular impermeability and uptake of biocides and antibiotics in Gram-negative bacteria

Denyer, Stephen Paul; Maillard, Jean‐Yves

doi:10.1046/j.1365-2672.92.5s1.19.x

Cited by 217 publications

(175 citation statements)

References 90 publications

(138 reference statements)

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“…It is known that an optimal hydrophilic-lipophilic balance (HLB) may enable best penetration across Gram-negative outer membrane [33][34][35] ; therefore, a polar moiety lowering the ClogP can be used to facilitate penetration through S. typhimurium cell wall; (b) serine racemase, a PLPdependent enzyme that shows a good structural similarity with OASS, is inhibited by a series of dicarboxylic derivatives such as modified malonates 36,37 ; (c) the synthetic protocol allowing to prepare such compounds is well established and high structural variability can be obtained starting from easily available materials. First, we synthesized two close analogs of 30, which are compounds 25 and 21, in order to assess whether the carboxylic moiety would better work as an ester or an acid.…”

Section: Rational Design and Sar Of Oass Inhibitorsmentioning

confidence: 99%

Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation ofO-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR

Annunziato¹,

Pieroni²,

Benoni

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Cysteine is a building block for many biomolecules that are crucial for living organisms. O-Acetylserine sulfhydrylase (OASS), present in bacteria and plants but absent in mammals, catalyzes the last step of cysteine biosynthesis. This enzyme has been deeply investigated because, beside the biosynthesis of cysteine, it exerts a series of ''moonlighting'' activities in bacteria. We have previously reported a series of molecules capable of inhibiting Salmonella typhimurium (S. typhymurium) OASS isoforms at nanomolar concentrations, using a combination of computational and spectroscopic approaches. The cyclopropane-1,2-dicarboxylic acids presented herein provide further insights into the binding mode of small molecules to OASS enzymes. Saturation transfer difference NMR (STD-NMR) was used to characterize the molecule/ enzyme interactions for both OASS-A and B. Most of the compounds induce a several fold increase in fluorescence emission of the pyridoxal 5 0 -phosphate (PLP) coenzyme upon binding to either OASS-A or OASS-B, making these compounds excellent tools for the development of competition-binding experiments.

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Section: Rational Design and Sar Of Oass Inhibitorsmentioning

confidence: 99%

Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation ofO-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR

Annunziato¹,

Pieroni²,

Benoni

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Therefore the penetration of a biocide or antibiotic may often be determined by its physical properties rather than its specific structure. An optimal hydrophilic-lipophilic balance will enable the best penetration across the outer membrane and a complex mix of portioning and passive diffusion processes is thus likely to determine the progress of a biocide across the Gram-negative outer envelope [59]. It is therefore likely that the coordination of Ag(I) to the coumarin-4-carboxylate ligands results in a biocide with suitable physical properties which are capable of penetration of the outer membrane.…”

Section: Antimicrobial Activity Of Coumarin Ligands and Their Ag(i) Cmentioning

confidence: 99%

Isolation and characterisation of silver(I) complexes of substituted coumarin-4-carboxylates which are effective against Pseudomonas aeruginosa biofilms

et al. 2014

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a b s t r a c tA novel series of coumarin-4-carboxylate ligands (2a-2l), their Ag(I) complexes (3a-3l) together with a number of their phenanthroline adducts (4d, 4f and 4g) have been synthesised and characterised. The ligands were prepared by either acid or base hydrolysis of their corresponding esters or by demethylation of a methylated acid derivative. The esters (1a-1i) were synthesised by an aromatic electrophilic substitution reaction between the conjugate base of substituted phenols and a vinyltriphenylphosphonium salt. The novel series of Ag(I) carboxylate complexes were prepared by reaction of silver nitrate with the coumarin ligands in aqueous/alcohol solution. The Ag(I) phenanthroline adducts were prepared by reaction of the Ag(I) complex with 1,10-phenanthroline in aqueous/alcohol solution. A selection of complexes were screened for their in vitro antibacterial activity against Pseudomonas aeruginosa grown planktonically or as a biofilm as well as a number of other clinically important strains, Escherichia coli, MRSA and Staphylococcus aureus. The activity against the P. aeruginosa biofilm was found to be significantly greater than against the planktonic bacteria.

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“…For example, the waxy, lipid-rich outer layers of mycobacteria render these organisms more resistant to killing by antimicrobial compounds. Gram-negative bacteria are protected from antibiotics by the negatively charged lipopolysaccharides in their outer membrane, which limit the entry of hydrophobic antibiotics into the cell [15]. While small, hydrophilic molecules can cross the membrane through non-specific porins, larger, more hydrophobic compounds, such as siderophores and vitamins, can only enter the cell through specialized porins.…”

Section: Cell Permeabilitymentioning

confidence: 99%

Why are bacteria refractory to antimicrobials?

Hogan

Kolter

2002

Current Opinion in Microbiology

142

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Cellular impermeability and uptake of biocides and antibiotics in Gram-negative bacteria

Cited by 217 publications

References 90 publications

Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation ofO-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR

Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation ofO-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR

Isolation and characterisation of silver(I) complexes of substituted coumarin-4-carboxylates which are effective against Pseudomonas aeruginosa biofilms

Why are bacteria refractory to antimicrobials?

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