Intracellular demography and the dynamics of Salmonella enterica infections.

An understanding of within-host dynamics of pathogen interactions with eukaryotic cells can shape the development of effective preventive measures and drug regimes. Such investigations have been hampered by the difficulty of identifying and observing directly, within live tissues, the multiple key variables that underlay infection processes. Fluorescence microscopy data on intracellular distributions of Salmonella enterica serovar Typhimurium (S. Typhimurium) show that, while the number of infected cells increases with time, the distribution of bacteria between cells is stationary (though highly skewed). Here, we report a simple model framework for the intensity of intracellular infection that links the quasi-stationary distribution of bacteria to bacterial and cellular demography. This enables us to reject the hypothesis that the skewed distribution is generated by intrinsic cellular heterogeneities, and to derive specific predictions on the within-cell dynamics of Salmonella division and host-cell lysis. For within-cell pathogens in general, we show that within-cell dynamics have implications across pathogen dynamics, evolution, and control, and we develop novel generic guidelines for the design of antibacterial combination therapies and the management of antibiotic resistance.

Intracellular demography and the dynamics of Salmonella enterica infections.

An understanding of within-host dynamics of pathogen interactions with eukaryotic cells can shape the development of effective preventive measures and drug regimes. Such investigations have been hampered by the difficulty of identifying and observing directly, within live tissues, the multiple key variables that underlay infection processes. Fluorescence microscopy data on intracellular distributions of Salmonella enterica serovar Typhimurium (S. Typhimurium) show that, while the number of infected cells increases with time, the distribution of bacteria between cells is stationary (though highly skewed). Here, we report a simple model framework for the intensity of intracellular infection that links the quasi-stationary distribution of bacteria to bacterial and cellular demography. This enables us to reject the hypothesis that the skewed distribution is generated by intrinsic cellular heterogeneities, and to derive specific predictions on the within-cell dynamics of Salmonella division and host-cell lysis. For within-cell pathogens in general, we show that within-cell dynamics have implications across pathogen dynamics, evolution, and control, and we develop novel generic guidelines for the design of antibacterial combination therapies and the management of antibiotic resistance.

Tomorrow's cities - a framework for building resilience

Urbanisation is the great driving force of the twenty-first century. Cities are associated with both productivity and creativity, and the benefits offered by closely connected and high density living and working contribute to sustainability. At the same time, cities need extensive infrastructure – like water, power, sanitation and transportation systems – to operate effectively. Cities therefore comprise multiple components, forming both static and dynamic systems that are interconnected directly and indirectly on a number of levels, all forming the backdrop for the interaction of people and processes. Bringing together large numbers of people and complex products in rich interactions can lead to vulnerability from hazards, threats and even trends, whether natural hazards, epidemics, political upheaval, demographic changes, economic instability and/or mechanical failures; The key to countering vulnerability is the identification of critical systems and clear understanding of their interactions and dependencies. Critical systems can be assessed methodically to determine the implications of their failure and their interconnectivities with other systems to identify options. The overriding need is to support resilience – defined here as the degree to which a system or systems can continue to function effectively in a changing environment. Cities need to recognise the significance of devising adaptation strategies and processes to address a multitude of uncertainties relating to climate, economy, growth and demography. In this paper we put forward a framework to support cities in understanding the hazards, threats and trends that can make them vulnerable to unexpected changes and unpredictable shocks. The framework draws on an asset model of the city, in which components that contribute to resilience include social capital, economic assets, manufactured assets, and governance. The paper reviews the field, and draws together an overarching framework intended to help cities plan a robust trajectory towards increased resilience through flexibility, resourcefulness and responsiveness. It presents some brief case studies demonstrating the applicability of the proposed framework to a wide variety of circumstances.