Caspase-3-dependent phagocyte death during systemic Salmonella enterica serovar Typhimurium infection of mice.

Growth of Salmonella enterica in mammalian tissues results from continuous spread of bacteria to new host cells. Our previous work indicated that infective S. enterica are liberated from host cells via stochastic necrotic burst independently of intracellular bacterial numbers. Here we report that liver phagocytes can undergo apoptotic caspase-3-mediated cell death in vivo, with apoptosis being a rare event, more prevalent in heavily infected cells. The density-dependent apoptotic cell death is likely to constitute an alternative mechanism of bacterial spread as part of a bet-hedging strategy, ensuring an ongoing protective intracellular environment in which some bacteria can grow and persist.

Modelling within-host spatiotemporal dynamics of invasive bacterial disease

Mechanistic determinants of bacterial growth, death, and spread within mammalian hosts cannot be fully resolved studying a single bacterial population. They are also currently poorly understood. Here, we report on the application of sophisticated experimental approaches to map spatiotemporal population dynamics of bacteria during an infection. We analyzed heterogeneous traits of simultaneous infections with tagged Salmonella enterica populations (wild-type isogenic tagged strains [WITS]) in wild-type and gene-targeted mice. WITS are phenotypically identical but can be distinguished and enumerated by quantitative PCR, making it possible, using probabilistic models, to estimate bacterial death rate based on the disappearance of strains through time. This multidisciplinary approach allowed us to establish the timing, relative occurrence, and immune control of key infection parameters in a true host-pathogen combination. Our analyses support a model in which shortly after infection, concomitant death and rapid bacterial replication lead to the establishment of independent bacterial subpopulations in different organs, a process controlled by host antimicrobial mechanisms. Later, decreased microbial mortality leads to an exponential increase in the number of bacteria that spread locally, with subsequent mixing of bacteria between organs via bacteraemia and further stochastic selection. This approach provides us with an unprecedented outlook on the pathogenesis of S. enterica infections, illustrating the complex spatial and stochastic effects that drive an infectious disease. The application of the novel method that we present in appropriate and diverse host-pathogen combinations, together with modelling of the data that result, will facilitate a comprehensive view of the spatial and stochastic nature of within-host dynamics. © 2008 Grant et al.

Control theory and systems biology

Presenting a control-theoretic treatment of stoichiometric systems, ... local parametric sensitivity analysis, the two approaches yield identical results. ...

A matter of life and death: sociomateriality, information systems and critical care

Sociomateriality has been attracting growing attention in the Organization Studies and Information Systems literatures since 2007, with more than 140 journal articles now referring to the concept. Over 80 percent of these articles have been published since January 2011 and almost all cite the work of Orlikowski (2007, 2010; Orlikowski and Scott 2008) as the source of the concept. Only a few, however, address all of the notions that Orlikowski suggests are entailed in sociomateriality, namely materiality, inseparability, relationality, performativity, and practices, with many employing the concept quite selectively. The contribution of sociomateriality to these literatures is, therefore, still unclear. Drawing on evidence from an ongoing study of the adoption of a computer-based clinical information system in a hospital critical care unit, this paper explores whether the notions, individually and collectively, offer a distinctive and coherent account of the relationship between the social and the material that may be useful in Information Systems research. It is argued that if sociomateriality is to be more than simply a label for research employing a number of loosely related existing theoretical approaches, then studies employing the concept need to pay greater attention to the notions entailed in it and to differences in their interpretation.