5 research outputs found
Naturally mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation
Staphylococcus aureusis a major bacterial pathogen, which causes severe blood and tissue infections that frequently emerge by autoinfection with asymptomatically carried nose and skin populations. However, recent studies report that bloodstream isolates differ systematically from those found in the nose and skin, exhibiting reduced toxicity toward leukocytes. In two patients, an attenuated toxicity bloodstream infection evolved from an asymptomatically carried high-toxicity nasal strain by loss-of-function mutations in the gene encoding the transcription factor repressor of surface proteins (rsp). Here, we report that rsp knockout mutants lead to global transcriptional and proteomic reprofiling, and they exhibit the greatest signal in a genome-wide screen for genes influencing S. aureus survival in human cells. This effect is likely to be mediated in part via SSR42, a long-noncoding RNA. We show that rsp controls SSR42 expression, is induced by hydrogen peroxide, and is required for normal cytotoxicity and hemolytic activity. Rsp inactivation in laboratory- and bacteremia derived mutants attenuates toxin production, but up-regulates other immune subversion proteins and reduces lethality during experimental infection. Crucially, inactivation of rsp preserves bacterial dissemination, because it affects neither formation of deep abscesses in mice nor survival in human blood. Thus, we have identified a spontaneously evolving, attenuated-cytotoxicity, non hemolytic S. aureus phenotype, controlled by a pleiotropic transcriptional regulator/noncoding RNA virulence regulatory system, capable of causing S. aureus bloodstream infections. Such a phenotype could promote deep infection with limited early clinical manifestations, raising concerns that bacterial evolution within the human body may contribute to severe infection
Violent victimisation, professional self-esteem, and punitivity of German police officers
Feminist Economics of Inequality, Development, and Growth
This study examines connections between intergroup inequality and macroeconomic outcomes, considering various channels through which gender, growth, and development interact. It upholds the salience not only of equality in opportunities but also equality in outcomes. The contribution argues that inequalities based on gender, race, ethnicity, and class undermine the ability to provision and expand capabilities, and it examines the macroeconomic policies that are likely to promote broadly shared development. It explores how the macroeconomy acts as a structure of constraint in achieving gender equality and in turn how gender relations in areas like education and wage gaps can have macro-level impacts. Further, it underscores that the interaction of the macroeconomy and gender relations depends on the structure of the economy, the nature of job segregation, the particular measure of gender inequality, and a country's international relations. Finally, it outlines policies for promoting gender equality as both an intrinsic goal and a step toward improving well-being.Development, growth, inequality, gender, macroeconomic policy, feminist economics, JEL CODES: 04, J3, E0, B54, D30,