Tuning the Effects of Bacterial Membrane Permeability through Photo‐Isomerization of Antimicrobial Cationic Amphiphiles

Salta, Joana; Benhamou, Raphael I.; Herzog, Ido M.; Fridman, Micha

doi:10.1002/chem.201703010

Cited by 20 publications

(14 citation statements)

References 35 publications

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“…To investigate the possible effects of compounds 1 and 4 on bacterial membrane integrity, we performed a propidium iodide (PI) test with S. aureus ATCC 29213 (strain H) treated with these CAM derivatives. 38 Cells with damaged membranes become permeable to PI and are stained with this red fluorescent dye. For the PI cell permability experiments, bacterial cells were incubated with either compound 1 or 4 at MIC for 1 h, after which the samples were stained with PI and visualized by fluorescence microscopy (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

Derivatives of Ribosome-Inhibiting Antibiotic Chloramphenicol Inhibit the Biosynthesis of Bacterial Cell Wall

et al. 2018

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Here, we describe the preparation and evaluation of α,β-unsaturated carbonyl derivatives of the bacterial translation inhibiting antibiotic chloramphenicol (CAM). Compared to the parent antibiotic, two compounds containing α,β-unsaturated ketones (1 and 4) displayed a broader spectrum of activity against a panel of Gram-positive pathogens with a minimum inhibitory concentration range of 2-32 μg/mL. Interestingly, unlike the parent CAM, these compounds do not inhibit bacterial translation. Microscopic evidence and metabolic labeling of a cell wall peptidoglycan suggested that compounds 1 and 4 caused extensive damage to the envelope of Staphylococcus aureus cells by inhibition of the early stage of cell wall peptidoglycan biosynthesis. Unlike the effect of membrane-disrupting antimicrobial cationic amphiphiles, these compounds did not rapidly permeabilize the bacterial membrane. Like the parent antibiotic CAM, compounds 1 and 4 had a bacteriostatic effect on S. aureus. Both compounds 1 and 4 were cytotoxic to immortalized nucleated mammalian cells; however, neither caused measurable membrane damage to mammalian red blood cells. These data suggest that the reported CAM-derived antimicrobial agents offer a new molecular scaffold for development of novel bacterial cell wall biosynthesis inhibiting antibiotics.

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Section: Resultsmentioning

confidence: 99%

Derivatives of Ribosome-Inhibiting Antibiotic Chloramphenicol Inhibit the Biosynthesis of Bacterial Cell Wall

et al. 2018

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“…Low cell membrane permeability and high rigidity are important countermeasures against cell wall–disruptive agents in other bacteria. This is often modulated by the ratios of saturated and unsaturated fatty acids within a membrane ( 33 , 34 ). We performed disk diffusion assays with a range of concentrations of SDS and scored susceptibility as a measure of the zone of inhibition.…”

Section: Resultsmentioning

confidence: 99%

MadR mediates acyl CoA-dependent regulation of mycolic acid desaturation in mycobacteria

Cooper

Peterson

Bailo

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Mycobacterium tuberculosis has a lipid-rich cell envelope that is remodeled throughout infection to enable adaptation within the host. Few transcriptional regulators have been characterized that coordinate synthesis of mycolic acids, the major cell wall lipids of mycobacteria. Here, we show that the mycolic acid desaturase regulator (MadR), a transcriptional repressor of the mycolate desaturase genes desA1 and desA2, controls mycolic acid desaturation and biosynthesis in response to cell envelope stress. A madR-null mutant of M. smegmatis exhibited traits of an impaired cell wall with an altered outer mycomembrane, accumulation of a desaturated α-mycolate, susceptibility to antimycobacterials, and cell surface disruption. Transcriptomic profiling showed that enriched lipid metabolism genes that were significantly down-regulated upon madR deletion included acyl-coenzyme A (aceyl-CoA) dehydrogenases, implicating it in the indirect control of β-oxidation pathways. Electromobility shift assays and binding affinities suggest a unique acyl-CoA pool–sensing mechanism, whereby MadR is able to bind a range of acyl-CoAs, including those with unsaturated as well as saturated acyl chains. MadR repression of desA1/desA2 is relieved upon binding of saturated acyl-CoAs of chain length C16 to C24, while no impact is observed upon binding of shorter chain and unsaturated acyl-CoAs. We propose this mechanism of regulation as distinct to other mycolic acid and fatty acid synthesis regulators and place MadR as the key regulatory checkpoint that coordinates mycolic acid remodeling during infection in response to host-derived cell surface perturbation.

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“…[137] The light-responsive feature of azo-based materials has been founded as a strategy to efficiently expose higher antibacterial activity under visible light exposure (λ > 400 nm trans-state) than UV light exposure (λ = 300-400 nm cis-state); one can speak of on-off antibacterial materials (Figure 15E). Although in most cases, the antibacterial efficacy of molecules with trans-state increases due to the more availability of their antibacterial agents, [138][139][140] in some cases, the molecules with cis-state perform better than their transstates; particularly the azobenzene groups carry carbohydrate or steroid moieties. [140][141][142] As well, in this study the intercalated azobenzene groups bearing antibacterial agents (i.e., imidazolium agents) inside the exfoliated montmorillonite nanosheets can act as antibacterial surfaces in cis-state (increased montmorillonite basal distance) due to the more availability of agents [129] Copyright 2019, Elsevier.…”

Section: E Coli S Aureusmentioning

confidence: 99%

Antimicrobial Ionic Liquid‐Based Materials for Biomedical Applications

Nikfarjam

Ghomi

Agarwal

et al. 2021

Adv Funct Materials

148

120

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Excessive and unwarranted administration of antibiotics has invigorated the evolution of multidrug-resistant microbes. There is, therefore, an urgent need for advanced active compounds. Ionic liquids with short-lived ion-pair structures are highly tunable and have diverse applications. Apart from their unique physicochemical features, the newly discovered biological activities of ionic liquids have fascinated biochemists, microbiologists, and medical scientists. In particular, their antimicrobial properties have opened new vistas in overcoming the current challenges associated with combating antibioticresistant pathogens. Discussions regarding ionic liquid derivatives in monomeric and polymeric forms with antimicrobial activities are presented here. The antimicrobial mechanism of ionic liquids and parameters that affect their antimicrobial activities, such as chain length, cation/anion type, cation density, and polymerization, are considered. The potential applications of ionic liquids in the biomedical arena, including regenerative medicine, biosensing, and drug/biomolecule delivery, are presented to stimulate the scientific community to further improve the antimicrobial efficacy of ionic liquids.

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Tuning the Effects of Bacterial Membrane Permeability through Photo‐Isomerization of Antimicrobial Cationic Amphiphiles

Cited by 20 publications

References 35 publications

Derivatives of Ribosome-Inhibiting Antibiotic Chloramphenicol Inhibit the Biosynthesis of Bacterial Cell Wall

Derivatives of Ribosome-Inhibiting Antibiotic Chloramphenicol Inhibit the Biosynthesis of Bacterial Cell Wall

MadR mediates acyl CoA-dependent regulation of mycolic acid desaturation in mycobacteria

Antimicrobial Ionic Liquid‐Based Materials for Biomedical Applications

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