Virulent Salmonella enterica infections can be exacerbated by concomitant infection of the host with a live attenuated S. enterica vaccine via Toll-like receptor 4-dependent interleukin-10 production with the involvement of both TRIF and MyD88.

During systemic disease in mice, Salmonella enterica grows intracellularly within discrete foci of infection in the spleen and liver. In concomitant infections, foci containing different S. enterica strains are spatially separated. We have investigated whether functional interactions between bacterial populations within the same host can occur despite the known spatial separation of the foci and independence of growth of salmonellae residing in different foci. In this study we have demonstrated that bacterial numbers of virulent S. enterica serovar Typhimurium C5 strain in mouse tissues can be increased by the presence of the attenuated aroA S. Typhimurium SL3261 vaccine strain in the same tissue. Disease exacerbation does not require simultaneous coinjection of the attenuated bacteria. SL3261 can be administered up to 48 hr after or 24 hr before the administration of C5 and still determine higher tissue numbers of the virulent bacteria. This indicates that intravenous administration of a S. enterica vaccine strain could potentially exacerbate an established infection with wild-type bacteria. These data also suggest that the severity of an infection with a virulent S. enterica strain can be increased by the prior administration of a live attenuated vaccine strain if infection occurs within 48 hr of vaccination. Exacerbation of the growth of C5 requires Toll-like receptor 4-dependent interleukin-10 production with the involvement of both Toll/interleukin-1 receptor-domain-containing adaptor inducing interferon-beta and myeloid differentiation factor 88.

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.

Bacterial growth rate and host factors as determinants of intracellular bacterial distributions in systemic Salmonella enterica infections.

Bacteria of the species Salmonella enterica cause a range of life-threatening diseases in humans and animals worldwide. The within-host quantitative, spatial, and temporal dynamics of S. enterica interactions are key to understanding how immunity acts on these infections and how bacteria evade immune surveillance. In this study, we test hypotheses generated from mathematical models of in vivo dynamics of Salmonella infections with experimental observation of bacteria at the single-cell level in infected mouse organs to improve our understanding of the dynamic interactions between host and bacterial mechanisms that determine net growth rates of S. enterica within the host. We show that both bacterial and host factors determine the numerical distributions of bacteria within host cells and thus the level of dispersiveness of the infection.

Measurements of thermal radiation in ultralight metal foams with open cells

Highly porous ultralightweight cellular metal foams with open cells have attractive mechanical, thermal, acoustic and other properties and are currently being exploited for high-temperature applications (e.g. acoustic liners for combustion chambers). In such circumstances, thermal radiation in the metal foam becomes a significant mechanism of heat transfer. This paper presents results from experimental measurements on radiative transfer in Fe-Cr-Al-Y (a steel-based high-temperature alloy) foams having high porosity (95 per cent) and different cell sizes, manufactured at low cost from the sintering route. The spectral transmittance and reflectance are measured at different infrared wavelengths ranging from 2.5 to 50 μm, which are subsequently used to determine the extinction coefficient and foam emissivity. The results show that the spectral quantities are strongly dependent on the wavelength, particularly in the short-wavelength regime (less than 25 μm). While the extinction coefficient decreases with increasing cell size, the effect of cell size on foam reflectance is not significant. When the temperature is increased, the total extinction coefficient increases but the total reflectance decreases. The effective radiative conductivity of the metal foam is obtained by using the guarded hot-plate apparatus. With the porosity fixed, the effective radiative conductivity increases with increasing cell size and increasing temperature. © IMechE 2004.

Thermal radiation in ultralight metal foams with open cells

This paper presents results from experimental measurements on radiative transfer in FeCrAlY (a steel based high temperature alloy) foams having high porosity (95%) and different cell sizes, manufactured at low cost from the sintering route. The spectral transmittance and reflectance are measured at different infrared wavelengths ranging from 2.5 to 50 μm, which are subsequently used to determine the extinction coefficient and foam emissivity. The results show that the spectral quantities are strongly dependent on the wavelength, particularly in the short wavelength regime (<25 μm). Whilst the extinction coefficient decreases with increasing cell size, the effect of cell size on foam reflectance is not significant. When the temperature is increased, the total extinction coefficient increases but the total reflectance decreases. An analytical model based on geometric optics laws, diffraction theory and metal foam morphology is developed to predict the radiative transfer, with cell size (or cell ligament diameter) and porosity identified as the two key parameters that dictate the foam radiative properties. Close agreement between the predicted effective foam conductivity due to radiation alone and that measured is observed. At fixed porosity, the radiative conductivity of the metal foam increases with increasing cell size and temperature. © 2004 Elsevier Ltd.All rights reserved.

Spread of Salmonella enterica in the body during systemic infection: unravelling host and pathogen determinants.

Salmonella enterica causes a range of life-threatening diseases in humans and animals worldwide. Current treatments for S. enterica infections are not sufficiently effective, and there is a need to develop new vaccines and therapeutics. An understanding of how S. enterica spreads in tissues has very important implications for targeting bacteria with vaccine-induced immune responses and antimicrobial drugs. Development of new control strategies would benefit from a more sophisticated evaluation of bacterial location, spatiotemporal patterns of spread and distribution in the tissues, and sites of microbial persistence. We review here recent studies of S. enterica serovar Typhimurium (S. Typhimurium) infections in mice, an established model of systemic typhoid fever in humans, which suggest that continuous bacterial spread to new infection foci and host phagocytes is an essential trait in the virulence of S. enterica during systemic infections. We further highlight how infections within host tissues are truly heterogeneous processes despite the fact that they are caused by the expansion of a genetically homogeneous microbial population. We conclude by discussing how understanding the within-host quantitative, spatial and temporal dynamics of S. enterica infections might aid the development of novel targeted preventative measures and drug regimens.