117,605 research outputs found

    Accurate downdating of least squares solutions

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    Bjorck, A.; Park, H.; Elden, L.. (1992). Accurate downdating of least squares solutions. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/1859

    Immunoglobulin-binding domains of peptostreptococcal protein L enhance vaginal colonization of mice by Streptococcus gordonii

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    Protein L, an immunoglobulin-binding protein of some strains of the anaerobic bacterium Peptostreptococcus magnus, has been hypothesized to be a virulence determinant in bacterial vaginosis. In order to investigate the role of protein L in peptostreptococcal virulence, the Ig-binding domains of protein L were expressed at the surface of the human oral commensal Streptococcus gordonii. Recombinant streptococci were used in vaginal colonization experiments, and protein L-expressing S. gordonii demonstrated enhanced ability to colonize the vaginal mucosa. Compared to the control strain, they also persisted for a longer period in the murine vagina

    The regulator PerR is involved in oxidative stress response and iron uptake and is necessary for full virulence in Streptococcus pyogenes

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    Ferric uptake regulator (Fur) and Fur-like proteins form an important family of transcriptional regulators in many bacterial species. In this work we have characterized a Fur-like protein, the peroxide regulator PerR, in an M1 serotype of Streptococcus pyogenes. To determine the role of PerR in S. pyogenes, we inactivated the gene by allelic replacement. PerR-deficient bacteria showed 48% reduction of (55)Fe incorporation from the culture medium. Transcriptional analysis revealed that mtsA, encoding a metal-binding protein of an ABC transporter in S. pyogenes, was transcribed at lower levels than were wild-type cells. Although total iron accumulation was reduced, the growth of the mutant strain was not significantly hampered. The mutant showed hyperresistance to hydrogen peroxide, and this response was induced in wild-type cells by growth in aerobiosis, suggesting that PerR acts as an oxidative stress-responsive repressor. PerR may also participate in the response to superoxide stress, as the perR mutant was more sensitive to the superoxide anion and had a reduced transcription of sodA, which encodes the sole superoxide dismutase of S. pyogenes. Complementation of the mutation with a functional perR gene restored (55)Fe incorporation, response to peroxide stress, and transcription of both mtsA and sodA to levels comparable to those of wild-type bacteria. Finally, the perR mutant was attenuated in virulence in a murine air sac model of infection (P < 0.05). These results demonstrate that PerR is involved in the regulation of iron homeostasis and oxidative stress responses and that it contributes to the virulence of S. pyogenes

    MtsABC is important for manganese and iron transport, oxidative stress resistance, and virulence of Streptococcus pyogenes

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    MtsABC is a Streptococcus pyogenes ABC transporter which was previously shown to be involved in iron and zinc accumulation. In this study, we showed that an mtsABC mutant has impaired growth, particularly in a metal-depleted medium and an aerobic environment. In metal-depleted medium, growth was restored by the addition of 10 microM MnCl(2), whereas other metals had modest or no effect. A characterization of metal radioisotope accumulation showed that manganese competes with iron accumulation in a dose-dependent manner. Conversely, iron competes with manganese accumulation but to a lesser extent. The mutant showed a pronounced reduction (>90%) of (54)Mn accumulation, showing that MtsABC is also involved in Mn transport. Using paraquat and hydrogen peroxide to induce oxidative stress, we show that the mutant has an increased susceptibility to reactive oxygen species. Moreover, activity of the manganese-cofactored superoxide dismutase in the mutant is reduced, probably as a consequence of reduced intracellular availability of manganese. The enzyme functionality was restored by manganese supplementation during growth. The mutant was also attenuated in virulence, as shown in animal experiments. These results emphasize the role of MtsABC and trace metals, especially manganese, for S. pyogenes growth, susceptibility to oxidative stress, and virulence
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