The synergistic effect of EDTA/antimicrobial combinations on Pseudomonas aeruginosa

Lambert, R. H.; Hanlon, G. W.; Denyer, Stephen Paul

doi:10.1046/j.1365-2672.2004.02135.x

Cited by 101 publications

(79 citation statements)

References 18 publications

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“…15 Earlier studies have shown that EDTA at 50 mM is useful in disrupting the biofilm. 16,17 Contrary to this, we noted that EDTA at 10 mM was found to be effective in disruption of bacterial biofilm when used alone. A large number of antibiotics and their combinations are available in the market.…”

contrasting

confidence: 66%

Role of EDTA and CSE1034 in curli formation and biofilm eradication of Klebsiella pneumoniae: a comparison with other drugs

Chaudhary

Payasi

2012

J Antibiot

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contrasting

confidence: 66%

Role of EDTA and CSE1034 in curli formation and biofilm eradication of Klebsiella pneumoniae: a comparison with other drugs

Chaudhary

Payasi

2012

J Antibiot

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“…Although prolonged treatments with EDTA are lethal, short treatments increase the permeability of the outer membrane to hydrophobic molecules (25,29). Thus, there can be synergy between EDTA and other antibacterial agents (2,8,24). In this study we report that EDTA not only kills P. aeruginosa planktonic cells but also affects P. aeruginosa biofilms ( Fig.…”

Section: Discussionmentioning

confidence: 56%

Chelator-Induced Dispersal and Killing of Pseudomonas aeruginosa Cells in a Biofilm

Banin

Brady

Greenberg

2006

Appl Environ Microbiol

439

379

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Biofilms consist of groups of bacteria attached to surfaces and encased in a hydrated polymeric matrix. Bacteria in biofilms are more resistant to the immune system and to antibiotics than their free-living planktonic counterparts. Thus, biofilm-related infections are persistent and often show recurrent symptoms. The metal chelator EDTA is known to have activity against biofilms of gram-positive bacteria such as Staphylococcus aureus. EDTA can also kill planktonic cells of Proteobacteria like Pseudomonas aeruginosa. In this study we demonstrate that EDTA is a potent P. aeruginosa biofilm disrupter. In Tris buffer, EDTA treatment of P. aeruginosa biofilms results in 1,000-fold greater killing than treatment with the P. aeruginosa antibiotic gentamicin. Furthermore, a combination of EDTA and gentamicin results in complete killing of biofilm cells. P. aeruginosa biofilms can form structured mushroom-like entities when grown under flow on a glass surface. Time lapse confocal scanning laser microscopy shows that EDTA causes a dispersal of P. aeruginosa cells from biofilms and killing of biofilm cells within the mushroom-like structures. An examination of the influence of several divalent cations on the antibiofilm activity of EDTA indicates that magnesium, calcium, and iron protect P. aeruginosa biofilms against EDTA treatment. Our results are consistent with a mechanism whereby EDTA causes detachment and killing of biofilm cells.Biofilms consist of groups of bacteria attached to surfaces and encased in a hydrated polymeric matrix. Bacterial biofilms are abundant in the environment and are involved in several human bacterial infections (reviewed in references 11, 14, and 31). Of medical importance, biofilms can withstand host immune responses (19)(20)(21) and are much more resistant to antibiotic treatments than their nonattached, individual, free-living (planktonic) counterparts (28,36). For these reasons, biofilm infections are persistent, and individuals often show recurring symptoms following antibiotic therapy. One of the best-studied models for biofilm formation is the bacterium Pseudomonas aeruginosa (reviewed in references 27 and 30), which causes many types of infections, including biofilm-associated chronic lung infections in cystic fibrosis patients, acute ulcerative keratitis in users of extended-wear soft contact lenses, and bacteremia in severe-burn victims.The metal chelator EDTA has been shown to cause lysis, loss of viability, and increased sensitivity of planktonic Proteobacteria to a variety of antibacterial agents (reference 13; reviewed in references 25, 29, and 40). This has led to the use of EDTA as a preservative in many products. Little is known about the influence of EDTA on biofilms of Proteobacteria. Raad et al. (32,33) have shown that EDTA combined with minocycline is an effective treatment for microorganisms embedded in biofilms on catheter surfaces. Their studies focused on Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans; however, they also reported two cases of...

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“…EDTA, a preservative in the food, drug, and cosmetic industries (16,22,28,31,43,60), has been shown to potentiate the antibiotic activity of nanoemulsions containing CPC against Gram-positive and Gram-negative bacteria. Farca et al have shown the synergistic effect of EDTA with five antimicrobial agents, ampicillin, cephalexin, oxytetracycline, streptomycin, and sulfadimethoxine, on three clinically isolated Gram-positive bacteria (Staphylococcus aureus, Staphylococcus hominis, and Enterococcus faecium) even in the absence of nanoemulsion delivery (16).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antibacterial Activity of NB-003 against Propionibacterium acnes

Pannu

McCarthy

Martin

et al. 2011

Antimicrob Agents Chemother

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NB-003 and NB-003 gel formulations are oil-in-water nanoemulsions designed for use in bacterial infections. In vitro susceptibility of Propionibacterium acnes to NB-003 formulations and comparator drugs was evaluated. Both NB-003 formulations were bactericidal against all P. acnes isolates, including those that were erythromycin, clindamycin, and/or tetracycline resistant. In the absence of sebum, the MIC 90 s/minimum bactericidal concentrations (MBC 90 s) for NB-003, NB-003 gel, salicylic acid (SA), and benzoyl peroxide (BPO) were 0.5/2.0, 1.0/2.0, 1,000/2,000, and 50/200 g/ml, respectively. In the presence of 50% sebum, the MIC 90 s/MBC 90 s of NB003 and BPOs increased to 128/1,024 and 400/1,600 g/ml, respectively. The MIC 90 s/MBC 90 s of SA were not significantly impacted by the presence of sebum. A reduction in the MBC 90 s for NB-003 and BPO was observed when 2% SA or 0.5% BPO was integrated into the formulation, resulting in MIC 90 s/MBC 90 s of 128/256 g/ml for NB003 and 214/428 g/ml for BPO. The addition of EDTA enhanced the in vitro efficacy of 0.5% NB-003 in the presence or absence of 25% sebum. The addition of 5 mM EDTA to each well of the microtiter plate resulted in a >16-and >256-fold decrease in MIC 90 and MBC 90 , yielding a more potent MIC 90 /MBC 90 of <1/<1 g/ml. The kinetics of bactericidal activity of NB-003 against P. acnes were compared to those of a commercially available product of BPO. Electron micrographs of P. acnes treated with NB-003 showed complete disruption of bacteria. Assessment of spontaneous resistance of P. acnes revealed no stably resistant mutant strains.

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The synergistic effect of EDTA/antimicrobial combinations on Pseudomonas aeruginosa

Cited by 101 publications

References 18 publications

Role of EDTA and CSE1034 in curli formation and biofilm eradication of Klebsiella pneumoniae: a comparison with other drugs

Role of EDTA and CSE1034 in curli formation and biofilm eradication of Klebsiella pneumoniae: a comparison with other drugs

Chelator-Induced Dispersal and Killing of Pseudomonas aeruginosa Cells in a Biofilm

In Vitro Antibacterial Activity of NB-003 against Propionibacterium acnes

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