Lidocaine Hydrochloride and Acetylsalicylate Kill Bacteria by Disrupting the Bacterial Membrane Potential in Different Ways

Ohsuka, Shinji; Ohta, Michio; Masuda, Koji; Arakawa, Yoshichika; Kaneda, Toshio; Kato, Naoya

doi:10.1111/j.1348-0421.1994.tb01803.x

Cited by 39 publications

(17 citation statements)

References 29 publications

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“…Other compounds had only limited effects, if any, on the susceptibility levels of PAO1 to these antibiotics. Interestingly, tetracain demonstrated strong synergism with novobiocin, a property already noted for some other local anesthetics (22,37). These results confirm that efficient permeabilizers may produce sufficient damage to the outer membrane bilayer to increase strongly the penetration of lipophilic antibiotics via the LPS uptake route (36,53).…”

supporting

confidence: 68%

“…The following agents, some of which have been suspected to permeabilize the outer membrane of gram-negative bacteria, were screened for potential cell surface activity in the absence of competing cations: acetylsalicylate (18,37), amiloride (20), ascorbate (18), azithromycin (9), ceftazidime, cetrimide (18), ciprofloxacin, crystal violet, erythromycin, fosfomycin, imipenem, nalidixic acid, p-aminobenzoate (43), pefloxacin, rifabutin, rifampin, sodium azide, tetracycline, trimethoprim, and vancomycin (8). None of these agents exhibited a noticeable action on the permeability of PAO1 cells to testosterone when assayed at 100 M (final concentration) (P Յ 130 nm s Ϫ1 ).…”

mentioning

confidence: 99%

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Use of steroids to monitor alterations in the outer membrane of Pseudomonas aeruginosa

Plésiat¹,

Aires²,

Godard³

et al. 1997

J Bacteriol

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Testosterone (a strongly hydrophobic steroid) and testosterone hemisuccinate (a negatively charged derivative) were used as probes to investigate alterations in the outer membrane of Pseudomonas aeruginosa. Diffusion rates of the steroids across the lipid bilayer were measured by coupling the influx of these compounds to their subsequent oxidation by an intracellular ⌬ 1 -dehydrogenase enzyme. Wild-type cells of P. aeruginosa (strain PAO1) were found to be 25 times more permeable to testosterone than to testosterone hemisuccinate. The uptake of the latter compound appeared to be partially dependent on the external pH, thus suggesting a preferential diffusion of the uncharged protonated form across the cell envelope. Using various PAO mutants, we showed that the permeation of steroids was not affected by overexpression of active efflux systems but was increased up to 5.5-fold when the outer membrane contained defective lipopolysaccharides or lacked the major porin OprF. Such alterations in the hydrophobic uptake pathway were not, however, associated with an enhanced permeability of the mutants to the small hydrophilic molecule N,N,N,N-tetramethyl-p-phenylene diamine. Thirty-six agents were also assayed for their ability to damage the cell surface of strain PAO1, using testosterone as a probe. Polymyxins, rBPI 23 , chlorhexidine, and dibromopropamidine demonstrated the strongest permeabilizing activities on a molar basis in the presence of 1 mM MgCl 2 . These amphiphilic polycations increased the transmembrane diffusion of testosterone up to 50-fold and sensitized the PAO1 cells to hydrophobic antibiotics. All together, these data indicated that the steroid uptake assay provides a direct and accurate measurement of the hydrophobic uptake pathway in P. aeruginosa.

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supporting

confidence: 68%

mentioning

confidence: 99%

Use of steroids to monitor alterations in the outer membrane of Pseudomonas aeruginosa

Plésiat¹,

Aires²,

Godard³

et al. 1997

J Bacteriol

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“…It has been reported that lidocaine has rapidly inhibited the generation of membrane potential in the inverted membrane vesicles of bacteria. It has been suggested that inhibition of membrane potential might contribute to the killing of bacteria, and that outer membrane changes might facilitate access to the inner membrane as a major target of killing (Garlid and Nakashima, 1983;Ohsuka et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

Structure–antimicrobial Properties Study of Some Dibasic Phenylcarbamic Acid Esters

Malík

Csöllei

Bukovský

2016

Indonesian J. Pharm.

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ABSTRAC TDue to worldwide phenomenon of microbial resistance to commonly used therapeutic agents, antibiotics and antifungals, dibasic di-/trimethylphenylcarbamic acid esters 1-3, a non--traditional series of potential antimicrobials, has been in vitro evaluated against chosen gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacterial strains as well as against yeast (C. albicans) by the minimu m inhibitory concentration (MIC) assay. Taking into consideration chemical structure of tested derivatives, the incorporation of more than one protonated atom of nitrogen into salt forming fragment positively influenced the activity against E. coli. On the contrary, the presence of one or more methyl groups instead of 3-alkoxy side chain attached to lipophilic aromatic moiety has not found to be favorable structural feature. In entire set of inspected compounds, the most promising results have been found for the compound 3, chemically 1-[3-piperidinium-1-yl-2-({[(2,4,6-trimethylphenyl)amino]carbonyl}oxy)propyl]piperidinium dichloride , against E. coli with the MIC=1.56mg/mL.

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“…They have been shown to bind to the membranes of bacteria, alter their structure and fluidity (20), and disrupt membrane potential (18). Procaine, like ethanol, has been shown to inhibit signal peptide cleavage (12).…”

Section: Effect Of Cell Wall Inhibitors On Pertussis Toxin Secretionmentioning

confidence: 99%

Antibacterial Agents and Release of Periplasmic Pertussis Toxin from Bordetella pertussis

Craig-Mylius

Weiss

2000

Antimicrob Agents Chemother

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Pertussis toxin accumulates in the periplasm of Bordetella pertussis prior to secretion, and we examined its fate following treatment with antimicrobial agents. Both antibiotics that inhibit protein synthesis (erythromycin and chloramphenicol), transcription (rifampin), or cell wall biosynthesis (cefoperazone and piperacillin) and magnesium sulfate (which inhibits transcription of pertussis toxin, but not bacterial growth) did not prevent release of preformed toxin. In contrast, agents that affect bacterial membranes, such as polymyxin B, lidocaine, procaine, and ethanol, inhibited release of preformed pertussis toxin. These results suggest new protein synthesis is not required for pertussis toxin secretion, but a functional membrane complex is required.Pertussis toxin is a member of the AB 5 family of toxins, which includes cholera toxin, Escherichia coli heat-labile toxin, and Shiga toxin. It is a critical virulence factor for the gramnegative bacterium Bordetella pertussis, the causative agent of whooping cough (21,22,32). It is also the most complex bacterial toxin known, comprised of six subunits, called S1, S2, S3, S4, and S5 in a 1:1:1:2:1 ratio (14,17,27). S1 is the A component of pertussis toxin, the part of the toxin that mediates damage to host cells. S1 enzymatically attaches the ADP-ribose group from NAD onto mammalian GTP binding proteins, abolishing normal cellular regulation. S2 to S5 associate to form the B component, or B pentamer, which binds to the host cell and delivers S1 into the cytoplasm of target cells.This complex structure of pertussis toxin seems to necessitate an equally complex pathway for assembly and secretion from the bacterium. Each of the toxin subunits is synthesized with an N-terminal signal sequence, which mediates secretion to the periplasm, where the signal peptide is removed and the subunits fold and assemble into holotoxin (17). Finally, secretion of the assembled toxin past the outer membrane is mediated by the proteins encoded by the ptl operon (PtlA through PtlI) (7, 33). Interestingly, AB 5 toxins have only been found in gram-negative bacteria. A possible explanation is that without the compartment provided by the periplasm of the gram-negative bacterium, the six toxin subunits would be unable to efficiently associate and assemble. Gram-positive bacteria lack this compartment and might release predominantly nonfunctional (and possibly immunizing) subunits.While the periplasm may be needed for efficient assembly of the AB 5 toxins, it can still act as a barrier to toxin secretion, and strains producing AB 5 toxins tend to accumulate intracellular pools of toxin. A dose as small as 0.05 to 0.15 ng of pertussis toxin per ml can elicit a positive response in the Chinese hamster ovary (CHO) cell assay (9, 33), and we have observed that B. pertussis accumulates hundreds of nanograms of periplasmic pertussis toxin, a potentially significant dose.We were interested in examining what happened to this pool of toxin during antibiotic treatment.In some situations, antibiotic tr...

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Lidocaine Hydrochloride and Acetylsalicylate Kill Bacteria by Disrupting the Bacterial Membrane Potential in Different Ways

Cited by 39 publications

References 29 publications

Use of steroids to monitor alterations in the outer membrane of Pseudomonas aeruginosa

Use of steroids to monitor alterations in the outer membrane of Pseudomonas aeruginosa

Structure–antimicrobial Properties Study of Some Dibasic Phenylcarbamic Acid Esters

Antibacterial Agents and Release of Periplasmic Pertussis Toxin from Bordetella pertussis

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