Chemical Properties of N-Chlorotaurine Sodium, a Key Compound in the Human Defence System

Gottardi, W.; Nagl, Markus

doi:10.1002/1521-4184(200212)335:9<411::aid-ardp411>3.0.co;2-d

Cited by 100 publications

(142 citation statements)

References 17 publications

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“…Adherence of bacteria to surfaces is mediated by proteins in S. aureus (16), S. epidermidis (2), and P. aeruginosa (17). Since NCT and analog substances recently have been shown to directly inactivate bacterial toxins (8,18), it seems likely that the detachment of biofilms by NCT is due to an impact on these adherence proteins via oxidation of thiols and aromatic and amino groups (4,5). To clarify the exact molecular sites of attack could be an interesting item in future studies.…”

Section: Discussionmentioning

confidence: 88%

“…The absence of the antimicrobial activity of micromolar NCT against P. aeruginosa biofilm in the recent study (11) might be explained by consumption of oxidative capacity by reducing moieties of the proteinaceous matrix of the biofilm (chlorine consumption [4,5]). However, the mild activity and high tolerability of N-chloro amino acids, particularly NCT, enable application of high concentrations to human tissue, which warrants a sufficient reserve of oxidation capacity despite some reduction (20).…”

Section: Discussionmentioning

confidence: 99%

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Bactericidal Activity of N -Chlorotaurine against Biofilm-Forming Bacteria Grown on Metal Disks

Coraça‐Huber

Ammann

Fille

et al. 2014

Antimicrob Agents Chemother

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Many orthopedic surgeons consider surgical irrigation and debridement with prosthesis retention as a treatment option for postoperative infections. Usually, saline solution with no added antimicrobial agent is used for irrigation. We investigated the activity of N-chlorotaurine (NCT) against various biofilm-forming bacteria in vitro and thereby gained significant information on its usability as a soluble and well-tolerated active chlorine compound in orthopedic surgery. Biofilms of Staphylococcus aureus were grown on metal alloy disks and in polystyrene dishes for 48 h. Subsequently, they were incubated for 15 min to 7 h in buffered solutions containing therapeutically applicable concentrations of NCT (1%, 0.5%, and 0.1%; 5.5 to 55 mM) at 37°C. NCT inactivated the biofilm in a time-and dose-dependent manner. Scanning electron microscopy revealed disturbance of the biofilm architecture by rupture of the extracellular matrix. Assays with reduction of carboxanilide (XTT) showed inhibition of the metabolism of the bacteria in biofilms. Quantitative cultures confirmed killing of S. aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa biofilms on metal alloy disks by NCT. Clinical isolates were slightly more resistant than ATCC type strains, but counts of CFU were reduced at least 10-fold by 1% NCT within 15 min in all cases. NCT showed microbicidal activity against various bacterial strains in biofilms. Whether this can be transferred to the clinical situation should be the aim of future studies.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Bactericidal Activity of N -Chlorotaurine against Biofilm-Forming Bacteria Grown on Metal Disks

Coraça‐Huber

Ammann

Fille

et al. 2014

Antimicrob Agents Chemother

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“…Two factors likely contribute to this stability. First, free amino acids, such as glycine, that possess amino and carboxylic acid groups on the ␣-carbon readily eliminate HCl from the N-chloramine, forming an imine (67). This unstable intermediate subsequently hydrolyzes to the aldehyde with release of ammonia.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, HOCl rapidly converts tyrosine and serine to p-hydroxyphenylacetaldehyde and glycoaldehyde (68), respectively, removing the oxidizing equivalent from the N-Cl bond while forming a reactive carbonyl. Second, the electron-withdrawing effects of the sulfonic acid group should stabilize the N-chloro derivative of taurine, a ␤-amino acid that does not readily form the imine (67). These factors suggest that N ⑀ -chloro-N ␣ -acetyllysine should be a more effective chlorinating agent than N-chloroglycine or N-chlorotaurine, which is what we observed when we exposed uracil to the various N-chloramines.…”

Section: Discussionmentioning

confidence: 99%

Myeloperoxidase Generates 5-Chlorouracil in Human Atherosclerotic Tissue

Takeshita

Byun

Nhan

et al. 2006

Journal of Biological Chemistry

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Somatic mutations induced by oxidative damage of DNA might play important roles in atherogenesis. However, the underlying mechanisms remain poorly understood. Myeloperoxidase, a heme protein expressed by select populations of artery wall macrophages, initiates one potentially mutagenic pathway by generating hypochlorous acid. This potent chlorinating agent reacts rapidly with primary amines to yield long-lived, selectively reactive N-chloramines. In the current studies, we demonstrate that myeloperoxidase produced by human macrophages differentiated in the presence of granulocyte macrophage colony-stimulating factor generates 5-chlorouracil, a mutagenic thymine analog. The primary amine taurine fails to block the reaction, suggesting that N-haloamines produced by macrophages might oxidize uracil. Model system studies demonstrated that N-chloramines convert uracil to 5-chlorouracil. Interestingly, the tertiary amine nicotine dramatically enhances uracil chlorination, suggesting that cigarette smoke might promote nucleobase oxidation by N-chloramines. To look for evidence that myeloperoxidase promotes uracil oxidation in vivo, we measured 5-chlorouracil levels in human aortic tissue, using isotope dilution gas chromatography-mass spectrometry. The level of 5-chlorouracil was 10-fold higher in atherosclerotic aortic tissue obtained during vascular surgery than in normal aortic tissue, suggesting that halogenated nucleobases produced by macrophages might contribute to atherogenesis. Because 5-chlorouracil can be incorporated into nuclear DNA, our observations raise the possibility that halogenation reactions initiated by phagocytes provide one pathway for mutagenesis, phenotypic modulation, and cytotoxicity during atherogenesis.

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“…N-Chlorotaurine (NCT) (molecular concentration, 181.57 g/mol) was prepared as crystalline sodium salt in our laboratory at pharmaceutical grade, as reported, and freshly dissolved in 0.1 M phosphate buffer (pH 7.1) for testing (24). Ammonium chloride (reagent grade) was from Merck (Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

N -Chlorotaurine Exhibits Fungicidal Activity against Therapy-Refractory Scedosporium Species and Lomentospora prolificans

Lackner

Binder

Reindl

et al. 2015

Antimicrob Agents Chemother

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N-Chlorotaurine (NCT), a well-tolerated endogenous long-lived oxidant that can be applied topically as an antiseptic, was tested on its fungicidal activity against Scedosporium and Lomentospora, opportunistic fungi that cause severe infections with limited treatment options, mainly in immunocompromised patients. In quantitative killing assays, both hyphae and conidia of Scedosporium apiospermum, Scedosporium boydii, and Lomentospora prolificans (formerly Scedosporium prolificans) were killed by 55 mM (1.0%) NCT at pH 7.1 and 37°C, with a 1-to 4-log 10 reduction in CFU after 4 h and a 4-to >6-log 10 reduction after 24 h. The addition of ammonium chloride to NCT markedly increased this activity. LIVE/DEAD staining of conidia treated with 1.0% NCT for 0.5 to 3 h increased the permeability of the cell wall and membrane. Preincubation of the test fungi in 1.0% NCT for 10 to 60 min delayed the time to germination of conidia by 2 h to >12 h and reduced their germination rate by 10.0 to 100.0%. Larvae of Galleria mellonella infected with 1.0 ؋ 10 7 conidia of S. apiospermum and S. boydii died at a rate of 90.0 to 100% after 8 to 12 days. The mortality rate was reduced to 20 to 50.0% if conidia were preincubated in 1.0% NCT for 0.5 h or if heat-inactivated conidia were used. Our study demonstrates the fungicidal activity of NCT against different Scedosporium and Lomentospora species. A postantifungal effect connected with a loss of virulence occurs after sublethal incubation times. The augmenting effect of ammonium chloride can be explained by the formation of monochloramine.

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Chemical Properties of N-Chlorotaurine Sodium, a Key Compound in the Human Defence System

Cited by 100 publications

References 17 publications

Bactericidal Activity of N -Chlorotaurine against Biofilm-Forming Bacteria Grown on Metal Disks

Bactericidal Activity of N -Chlorotaurine against Biofilm-Forming Bacteria Grown on Metal Disks

Myeloperoxidase Generates 5-Chlorouracil in Human Atherosclerotic Tissue

N -Chlorotaurine Exhibits Fungicidal Activity against Therapy-Refractory Scedosporium Species and Lomentospora prolificans

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