Macrophage Replication Screen Identifies a Novel Francisella Hydroperoxide Resistance Protein Involved in Virulence

Francisella tularensis is a Gram-negative facultative intracellular pathogen and the causative agent of tularemia. Recently, genome-wide screens have identified Francisella genes required for virulence in mice. However, the mechanisms by which most of the corresponding proteins contribute to pathogenesis are still largely unknown. To further elucidate the roles of these virulence determinants in Francisella pathogenesis, we tested whether each gene was required for replication of the model pathogen F. novicida within macrophages, an important virulence trait. Fifty-three of the 224 genes tested were involved in intracellular replication, including many of those within the Francisella pathogenicity island (FPI), validating our results. Interestingly, over one third of the genes identified are annotated as hypothetical, indicating that F. novicida likely utilizes novel virulence factors for intracellular replication. To further characterize these virulence determinants, we selected two hypothetical genes to study in more detail. As predicted by our screen, deletion mutants of FTN_0096 and FTN_1133 were attenuated for replication in macrophages. The mutants displayed differing levels of attenuation in vivo, with the FTN_1133 mutant being the most attenuated. FTN_1133 has sequence similarity to the organic hydroperoxide resistance protein Ohr, an enzyme involved in the bacterial response to oxidative stress. We show that FTN_1133 is required for F. novicida resistance to, and degradation of, organic hydroperoxides as well as resistance to the action of the NADPH oxidase both in macrophages and mice. Furthermore, we demonstrate that F. holarctica LVS, a strain derived from a highly virulent human pathogenic species of Francisella, also requires this protein for organic hydroperoxide resistance as well as replication in macrophages and mice. This study expands our knowledge of Francisella's largely uncharacterized intracellular lifecycle and demonstrates that FTN_1133 is an important novel mediator of oxidative stress resistance

Exploring Change in Small Firms’ HRM Practices

The academic literature widely acknowledges changes and variation in the practices of small firms but only a small amount of empirical work has explored the processes through which HRM practices undergo change. Research has tended, instead, to examine the presence and effectiveness of HRM in small firms and often viewed this in terms of a deficit model relating such practices to an understanding of HRM derived from larger firms. This chapter focuses on the recruitment and selection and staff payment practices in use in three small services firms to explore the everyday, ongoing detail of their HRM processes and practices. Identifying the different processes through which recruitment and selection and staff payment practices changed in the participant firms provides a base for discussing persistent forms of informality and the lack of stability that reflects the everyday realities of the firms, not only in contrast to their formalized policies but in engagement with them. This chapter advances understanding of selected HRM practices in small services firms after periods of formalisation and adoption of HRM policies and practices. The chapter also discusses how developing knowledge of small firms’ HRM practices in this way has implications for researchers and practitioners

Lebensrettende Maßnahmen bei Kindern („paediatric life support“): Kapitel 6 der Leitlinien zur Reanimation 2015 des European Resuscitation Council

SCOPUS: ar.jinfo:eu-repo/semantics/publishe