Increased permeability of the outer membrane of Escherichia coli induced by the dimer in compound 48/80.

Katsu, Takashi; Shibata, Mie; Fujita, Yuzuru

doi:10.1248/cpb.33.893

Cited by 5 publications

(4 citation statements)

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“…Efforts to sensitize selected gram-negative pathogens to EIPE-1 by chemically permeabilizing their outer membranes was attempted using the outer membrane permeabilizer compound 48/80 (Katsu et al, 1985) as described by Champlin et al (2005). Batch test cultures were prepared and cultivated as described above after treatment with outer membrane permeabilizer compound 48/80…”

Section: Outer Membrane Permeabilizationmentioning

confidence: 99%

“…In view of the hydrophobic nature of EIPE-1, its gram-positive antibacterial spectrum strongly suggests that the intrinsic resistance seen in disparate gram-negative pathogens is due to exclusion by virtue of the impermeability properties of their outer cell envelopes for nonpolar molecules. To test this possibility more specifically, the outer membrane permeabilizer compound 48/80 was administered to chemically disrupt the cell surfaces of selected gram-negative pathogens (Katsu et al, 1985;Champlin et al, 2005) in an effort to synergistically sensitize the organisms to EIPE-1. Data contained in Figure 6A show only slight to no synergistic sensitization due to treatment with compound 48/80 and EIPE-1 in any of the three gram-negative test bacteria at a permeabilizer concentration that effectively sensitized P. aeruginosa to the hydrophobic biocide triclosan (Figure 6B).…”

Section: Chemical Outer Membrane Permeabilizationmentioning

confidence: 99%

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Relationship between cell envelope ultrastructure and the antibacterial properties of a novel hydrophobic eumelanin-inspired derivative

Reed,

Nehmzow,

Essandoh

et al. 2023

Front. Bacteriol.

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IntroductionUnique impermeability properties of the gram-negative outer cell envelope typically render these organisms intrinsically resistant to hydrophobic antibacterial compounds. Eumelanin-inspired indoylenephenyleneethynylene (EIPE) compounds possess scaffolding to which functional groups were attached to potentially provide antibacterial properties in the forms of hydrophilic (EIPE-HCl) and hydrophobic (EIPE-1) derivatives.MethodsStandardized disk agar diffusion and microbroth dilution bioassays were employed to assess the susceptibility of disparate gram-negative and gram-positive bacterial pathogens to the two compounds. EIPE-1 mechanisms of action and intrinsic resistance were further investigated turbidimetrically in batch cultures with the aid of the gram-negative outer membrane permeabilizer compound 48/80.ResultsHydrophobic derivative EIPE-1 exhibited a gram-positive antibacterial spectrum, while hydrophilic derivative EIPE-HCl possessed no antibacterial properties. EIPE-1 exhibited minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values below 2.0 µg/mL against all gram-positive bacteria, including two methicillin-resistant strains. In contrast, MIC/MBC values greater than 128 µg/mL were obtained for all gram-negative bacteria examined. Susceptibility of two strains of the strict anaerobe Clostridioides difficile indicated the EIPE-1 mechanism of action does not require molecular oxygen. Turbidimetric growth curves revealed EIPE-1 induced rapid bacteriolysis of Bacillus subtilis ATCC 6633, thereby suggesting a membrane-directed modality. Lastly, the outer membrane permeabilizer compound 48/80 failed to markedly sensitize any of three phylogenetically disparate gram-negative organisms to EIPE-1.ConclusionThese data suggest that the hydrophobic melanin-inspired derivative EIPE-1 inhibits gram-positive bacteria in a cytoplasmic membrane-directed manner independent of oxygen. Moreover, a secondary mechanism may function concomitantly with outer membrane exclusionary properties to underly the intrinsic resistance of gram-negative pathogens.

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Section: Outer Membrane Permeabilizationmentioning

confidence: 99%

Section: Chemical Outer Membrane Permeabilizationmentioning

confidence: 99%

Relationship between cell envelope ultrastructure and the antibacterial properties of a novel hydrophobic eumelanin-inspired derivative

Reed,

Nehmzow,

Essandoh

et al. 2023

Front. Bacteriol.

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“…Meincke et al (1980) found that P. aeruginosa accumulated considerably more cell envelope-associated triclosan than did two other organisms, and yet was more resistant to its growth-inhibitory action. Compound 48/80 is a mixture of polymers formed from the condensation of p-methoxyphenethylmethylamine with formaldehyde (Katsu et al, 1985a), which effectively permeabilizes the gram-negative outer membrane to nonpolar compounds (Katsu et al, 1985b). Recent work from this laboratory (Champlin et al, 2005) revealed that P. aeruginosa can be sensitized to a low concentration (2.0 mg mL À1 ) of triclosan using compounds such as polymyxin B-nonapeptide, EDTA, and compound 48/80, which selectively permeabilize the gram-negative outer membrane (Hancock & Wong, 1984;Vaara, 1992).…”

Section: Introductionmentioning

confidence: 99%

“…Recent work from this laboratory (Champlin et al, 2005) revealed that P. aeruginosa can be sensitized to a low concentration (2.0 mg mL À1 ) of triclosan using compounds such as polymyxin B-nonapeptide, EDTA, and compound 48/80, which selectively permeabilize the gram-negative outer membrane (Hancock & Wong, 1984;Vaara, 1992). Compound 48/80 is a mixture of polymers formed from the condensation of p-methoxyphenethylmethylamine with formaldehyde (Katsu et al, 1985a), which effectively permeabilizes the gram-negative outer membrane to nonpolar compounds (Katsu et al, 1985b).…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of compound 48/80-sensitized Pseudomonas aeruginosa to the hydrophobic biocide triclosan

Ellison

Roberts

Champlin

2007

FEMS Microbiology Letters

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Pseudomonas aeruginosa is intrinsically resistant to the hydrophobic biocide triclosan, and yet it can be sensitized to low concentrations by permeabilization of the outer membrane using compound 48/80. A selective plating assay revealed that compound 48/80-permeabilized YM64, a triclosan-recognizing efflux pump-deficient variant, was unable to initiate growth on a medium containing triclosan. Macrobroth dilution assay data revealed that treatment with compound 48/80 synergistically decreased minimal inhibitory concentrations of the hydrophobic antibacterial agents rifamycin SV and chloramphenicol for all cell envelope variant strains examined. A low concentration of triclosan exerted a transient bactericidal effect on permeabilized wild-type strain PAO1, after which exponential growth resumed within 4 h. Permeabilized strain YM64 was unable to overcome the inhibition; yet, both strains remained susceptible to chloramphenicol for as long as 6 h, thereby suggesting that the outer membrane remained permeable to nonpolar compounds. These data support the notion that the transitory nature of compound 48/80 sensitization to triclosan in P. aeruginosa does not involve obviation of the hydrophobic diffusion pathway through the outer membrane. The inability of strain YM64 to overcome the synergistic effect of compound 48/80 and triclosan strongly suggests that triclosan-recognizing efflux pumps are involved in maintaining viability in wild-type cells whose outer membranes are otherwise compromised.

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Compromising the Protective Barrier of the Gram-Negative Bacterial Cell Surface

Reese¹,

Clancy²

1992

Emerging Targets in Antibacterial and Antifungal Chemotherapy

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Increased permeability of the outer membrane of Escherichia coli induced by the dimer in compound 48/80.

Cited by 5 publications

References 0 publications

Relationship between cell envelope ultrastructure and the antibacterial properties of a novel hydrophobic eumelanin-inspired derivative

Relationship between cell envelope ultrastructure and the antibacterial properties of a novel hydrophobic eumelanin-inspired derivative

Susceptibility of compound 48/80-sensitized Pseudomonas aeruginosa to the hydrophobic biocide triclosan

Compromising the Protective Barrier of the Gram-Negative Bacterial Cell Surface

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