During oxidative burst, neutrophils selectively generate HOCl to destroy invading microbial pathogens. Excess HOCl reacts with taurine, a semi-essential amino acid, resulting in the formation of the longer-lived biogenerated broad-spectrum antimicrobial agent, N-chlorotaurine (NCT). In the presence of an excess of HOCl or under moderately acidic conditions, NCT can be further chlorinated, or it can disproportionate to produce N,N-dichlorotaurine (NNDCT). In the present study, 2,2-dimethyltaurine was used to prepare a more stable N-chlorotaurine, namely, N,N-dichloro-2,2-dimethyltaurine (NVC-422). In addition, we report on the chemical characterization, in vitro antimicrobial properties, and cytotoxicity of this compound. NVC-422 was shown effectively to kill all 17 microbial strains tested, including antibiotic-resistant Staphylococcus aureus and Enterococcus faecium. The minimum bactericidal concentration of NVC-422 against Gram-negative and Grampositive bacteria ranged from 0.12 to 4 g/ml. The minimum fungicidal concentrations against Candida albicans and Candida glabrata were 32 and 16 g/ml, respectively. NVC-422 has an in vitro cytotoxicity (50% cytotoxicity ‫؍‬ 1,440 g/ml) similar to that of NNDCT. Moreover, our data showed that this agent possesses rapid, pH-dependent antimicrobial activity. At pH 4, NVC-422 completely killed both Escherichia coli and S. aureus within 5 min at a concentration of 32 g/ml. Finally, the effect of NVC-422 in the treatment of an E. coli-infected granulating wound rat model was evaluated. Treatment of the infected granulating wound with NVC-422 resulted in significant reduction of the bacterial tissue burden and faster wound healing compared to a saline-treated control. These findings suggest that NVC-422 could have potential application as a topical antimicrobial.As part of the innate immune system, leukocytes are capable of generating and releasing reactive oxygen species. During oxidative burst, neutrophils selectively generate hypochlorous acid to destroy invading microbial pathogens. In a secondary reaction, hypochlorous acid reacts with taurine, a semi-essential amino acid. The resulting N-chlorotaurine (NCT) is a wellknown antimicrobial and anti-inflammatory oxidant (12, 15). Furthermore, NCT has shown significant bactericidal and fungicidal properties with relatively low toxicity compared to other oxidants (13,14). In the presence of an excess of hypochlorous acid or under moderately acidic conditions, NCT can be further chlorinated or, alternatively, it can disproportionate to form N,N-dichlorotaurine (NNDCT), which also has broadspectrum antimicrobial activity (9). Unfortunately, both NCT and NNDCT have relatively short solution half-lives, decomposing by hydrolytic dehydrochlorination (5, 6, 16). Because of this instability, the potential usefulness of the endogenous Nchlorotaurines as marketable therapeutics is limited. Replacement of the hydrogens at the ␤-carbon of taurine by methyl groups prevents the dehydrochlorination process, thereby circumventing this instabi...

No abstract

No abstract

Wound healing depends on controlling bacterial balance while maintaining the viability of the healing tissues. In vitro toxicity indexes provide helpful guidelines subsequent to in vivo evaluations and clinical applications. The study findings suggest that NeutroPhase, in contrast with many commercially available wound cleansers, has rapid bactericidal activity at concentrations that are safe for human cells.

NVC-422 is an effective topical agent against S. aureus biofilms, with dose-dependent efficacy in this animal model of biofilm-associated sinusitis.

No abstract

An understanding of the mechanisms by which bacteria derive their energy is clearly important for the prediction of growth yields. Bacteria can synthesize ATP by a variety of routes, by fermentation, by oxidative phosphorylation, and possibly by the excretion of metabolic end products. The bacterium Escherichia coli has been studied extensively and a great deal is now known about the different membrane-bound multi-enzyme complexes that are responsible for oxidative phosphorylation. The efficiency of oxidative phosphorylation can vary not only between different bacteria that have adapted to particular ecological niches but also in an individual bacterium grown under different conditions or modified genetically by mutation with respect to its parent. Clearly, the concept that bacteria always grow with maximum thermodynamic efficiency is erroneous and it is important, therefore, to be able to assess the efficiency of energy conversion as well as the biochemical and genetical factors that regulate the physiological expression of energy-yielding reactions if they are to be manipulated by the investigator.

SUMMARYThe growth of the Hildenborough strain of Desulfovibrio vulgaris has been studied ill stirred cultures flushed withAr/CO2 (95 + 5)and H2/CO2 (95 q-5). Sodium lactate was used as the carbon-energy source with sodium sulphate as the terminal electron acceptor. The initial lactate concentration was varied in defined media (pH 7) augmented with 0.5 mM citrate as chelating agent, and growth was followed to completion. Yields were calculated for the region of strict lactate limitation, i.e. where the total growth was directly proportional to the initial lactate concentration.The maximum specific growth rate was identical for both gases (0.15 h -1) ; however, the yield under hydrogen was 25.8 :k 2.1 g/mole of lactate compared with 9.20 ~ 0.78 g/mole under argon (95% confidence limits). No growth occurred in the absence of sodium lactate. The total protein contents of the cells were similar in both cases (67-75 per cent).In addition the organism was grown under a hydrogen atmosphere ill medium augmented with 0.01 per cent yeast extract. This concentration of yeast extract was estimated to provide a sufficient exogenous supply of amino acids for cell biosynthesis at the expected levels of cell density. Although a significant increase in the growth rate was observed (0.20 h -1) the yield was only marginally improved (28.2 ± 2.7 g/mole) In the absence of lactate the residual growth (7 mg/1) was explained by the utilisation of substances in the yeast extract as energy source. Isobutanol was tested as an energy source under both nitrogen and hydrogen in media augmented with 0.02 per cent yeast extract. The marginal growth that occurred was again explained by the utilisation of some component of the yeast extract as energy source.