16 research outputs found

    Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

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    Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Ξ”lgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Ξ”lgt mutant had markedly reduced lipoprotein expression on the cell surface. The Ξ”lgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Ξ”lgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Ξ”lgt mutant were associated with only slightly delayed growth in complete medium. However the Ξ”lgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Ξ”lgt mutant from establishing invasive infection

    Communities And Health Policy: A Pathway For Change

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    Improving the health system can reduce the effects of health disparities, but it can do little to eliminate them. An upsurge in new research is documenting the impact of physical, social, and economic environmental factors: air quality, housing conditions, racism, relationship to community institutions, and neighborhood economic conditions, all of which affect health status over time. A combined focus on community and the policies that affect communities’ environments presents opportunities for altering and ameliorating the underlying forces at the heart of the determinants of health. This Perspective presents examples of successful community involvement and policy change

    Turning the Ship: Moving From Clinical Treatment to Environmental Prevention: A Health Disparities Policy Advocacy Initiative

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    Β· This article examines success factors for a statewide initiative to reduce health disparities by establishing environmental policies to reduce asthma risk factors for school-aged children. Β· Twelve local coalitions and a statewide network focused on schools, housing, and outdoor air policies. Β· Multiple types and levels of policy advocacy were encouraged by the Initiative so that issues at the local level linked to larger issues across the state, and conversely state-level policies supported local endeavors. Β· Factors that contributed to the success of the initiative included: structuring the initiative on a systems change model; employing multiple technical assistance providers to assure fidelity to the model, building capacity, facilitating strategic partnerships, and facilitating mid-course adjustments; communicating β€œintentional” policy outcomes from the foundation; and structuring an evaluation team to analyze multi-level data and provide feedback at all levels. Β· Local coalitions that developed meaningful community engagement and used data to educate policy makers were the most successful

    Communities And Health Policy: A Pathway For Change

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