143 research outputs found
In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide
<p>Abstract</p> <p>Background</p> <p>Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) produced by vaginal lactobacilli is generally believed to protect against bacteria associated with bacterial vaginosis (BV), and strains of lactobacilli that can produce H<sub>2</sub>O<sub>2 </sub>are being developed as vaginal probiotics. However, evidence that led to this belief was based in part on non-physiological conditions, antioxidant-free aerobic conditions selected to maximize both production and microbicidal activity of H<sub>2</sub>O<sub>2</sub>. Here we used conditions more like those <it>in vivo </it>to compare the effects of physiologically plausible concentrations of H<sub>2</sub>O<sub>2 </sub>and lactic acid on a broad range of BV-associated bacteria and vaginal lactobacilli.</p> <p>Methods</p> <p>Anaerobic cultures of seventeen species of BV-associated bacteria and four species of vaginal lactobacilli were exposed to H<sub>2</sub>O<sub>2</sub>, lactic acid, or acetic acid at pH 7.0 and pH 4.5. After two hours, the remaining viable bacteria were enumerated by growth on agar media plates. The effect of vaginal fluid (VF) on the microbicidal activities of H<sub>2</sub>O<sub>2 </sub>and lactic acid was also measured.</p> <p>Results</p> <p>Physiological concentrations of H<sub>2</sub>O<sub>2 </sub>(< 100 Ī¼M) failed to inactivate any of the BV-associated bacteria tested, even in the presence of human myeloperoxidase (MPO) that increases the microbicidal activity of H<sub>2</sub>O<sub>2</sub>. At 10 mM, H<sub>2</sub>O<sub>2 </sub>inactivated all four species of vaginal lactobacilli but only one of seventeen species of BV-associated bacteria. Moreover, the addition of just 1% vaginal fluid (VF) blocked the microbicidal activity of 1 M H<sub>2</sub>O<sub>2</sub>. In contrast, lactic acid at physiological concentrations (55-111 mM) and pH (4.5) inactivated all the BV-associated bacteria tested, and had no detectable effect on the vaginal lactobacilli. Also, the addition of 10% VF did not block the microbicidal activity of lactic acid.</p> <p>Conclusions</p> <p>Under optimal, anaerobic growth conditions, physiological concentrations of lactic acid inactivated BV-associated bacteria without affecting vaginal lactobacilli, whereas physiological concentrations of H<sub>2</sub>O<sub>2 </sub>produced no detectable inactivation of either BV-associated bacteria or vaginal lactobacilli. Moreover, at very high concentrations, H<sub>2</sub>O<sub>2 </sub>was more toxic to vaginal lactobacilli than to BV-associated bacteria. On the basis of these <it>in vitro </it>observations, we conclude that lactic acid, not H<sub>2</sub>O<sub>2</sub>, is likely to suppress BV-associated bacteria <it>in vivo</it>.</p
Carcinogenic Effects in a Phenylketonuria Mouse Model
Phenylketonuria (PKU) is a metabolic disorder caused by impaired phenylalanine hydroxylase (PAH). This condition results in hyperphenylalaninemia and elevated levels of abnormal phenylalanine metabolites, among which is phenylacetic acid/phenylacetate (PA). In recent years, PA and its analogs were found to have anticancer activity against a variety of malignancies suggesting the possibility that PKU may offer protection against cancer through chronically elevated levels of PA. We tested this hypothesis in a genetic mouse model of PKU (PAHenu2) which has a biochemical profile that closely resembles that of human PKU. Plasma levels of phenylalanine in homozygous (HMZ) PAHenu2 mice were >12-fold those of heterozygous (HTZ) littermates while tyrosine levels were reduced. Phenylketones, including PA, were also markedly elevated to the range seen in the human disease. Mice were subjected to 7,12 dimethylbenz[a]anthracene (DMBA) carcinogenesis, a model which is sensitive to the anticancer effects of the PA derivative 4-chlorophenylacetate (4-CPA). Tumor induction by DMBA was not significantly different between the HTZ and HMZ mice, either in total tumor development or in the type of cancers that arose. HMZ mice were then treated with 4-CPA as positive controls for the anticancer effects of PA and to evaluate its possible effects on phenylalanine metabolism in PKU mice. 4-CPA had no effect on the plasma concentrations of phenylalanine, phenylketones, or tyrosine. Surprisingly, the HMZ mice treated with 4-CPA developed an unexplained neuromuscular syndrome which precluded its use in these animals as an anticancer agent. Together, these studies support the use of PAHenu2 mice as a model for studying human PKU. Chronically elevated levels of PA in the PAHenu2 mice were not protective against cancer
Shaping the growth behaviour of biofilms initiated from bacterial aggregates
Bacterial biofilms are usually assumed to originate from individual cells
deposited on a surface. However, many biofilm-forming bacteria tend to
aggregate in the planktonic phase so that it is possible that many natural and
infectious biofilms originate wholly or partially from pre-formed cell
aggregates. Here, we use agent-based computer simulations to investigate the
role of pre-formed aggregates in biofilm development. Focusing on the initial
shape the aggregate forms on the surface, we find that the degree of spreading
of an aggregate on a surface can play an important role in determining its
eventual fate during biofilm development. Specifically, initially spread
aggregates perform better when competition with surrounding unaggregated
bacterial cells is low, while initially rounded aggregates perform better when
competition with surrounding unaggregated cells is high. These contrasting
outcomes are governed by a trade-off between aggregate surface area and height.
Our results provide new insight into biofilm formation and development, and
reveal new factors that may be at play in the social evolution of biofilm
communities
Highlights of the DNA cutters:a short history of the restriction enzymes
In the early 1950ās, āhost-controlled variation in bacterial virusesā was reported as a non-hereditary phenomenon: one cycle of viral growth on certain bacterial hosts affected the ability of progeny virus to grow on other hosts by either restricting or enlarging their host range. Unlike mutation, this change was reversible, and one cycle of growth in the previous host returned the virus to its original form. These simple observations heralded the discovery of the endonuclease and methyltransferase activities of what are now termed Type I, II, III and IV DNA restriction-modification systems. The Type II restriction enzymes (e.g. EcoRI) gave rise to recombinant DNA technology that has transformed molecular biology and medicine. This review traces the discovery of restriction enzymes and their continuing impact on molecular biology and medicine
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