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.

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.

A dynamic view of the spread and intracellular distribution of Salmonella enterica.

The events that determine the dynamics of proliferation, spread and distribution of microbial pathogens within their hosts are surprisingly heterogeneous and poorly understood. We contend that understanding these phenomena at a sophisticated level with the help of mathematical models is a prerequisite for the development of truly novel, targeted preventative measures and drug regimes. We describe here recent studies of Salmonella enterica infections in mice which suggest that bacteria resist the antimicrobial environment inside host cells and spread to new sites, where infection foci develop, and thus avoid local escalation of the adaptive immune response. We further describe implications for our understanding of the pathogenic mechanism inside the host.

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.

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.

Spatial determination of gold catalyst residue used in the production of ZnO nanowires by SIMS depth profiling analysis

In this paper we demonstrate how secondary ion mass spectrometry (SIMS) can be applied to ZnO nanowire structures for gold catalyst residue determination. Gold plays a significant role in determining the structural properties of such nanowires, with the location of the gold after growth being a strong indicator of the growth mechanism. For the material investigated here, we find that the gold remains at the substrate-nanowire interface. This was not anticipated as the usual growth mechanism associated with catalyst growth is of a vapour-liquid-solid (VLS) type. The results presented here favour a vapour-solid (VS) growth mechanism instead. Copyright © 2007 John Wiley & Sons, Ltd.

Environmental evaluation of localising production as a strategy for sustainable development: a case study of two consumer goods in Jamaica

The objective of this study was to compare the life-cycle environmental impacts of changed production structures for two consumer goods (high-density polyethylene (HDPE) shopping bags and beds) in Jamaica. A scenario technique was used to construct three alternative production structures for each product; each scenario reflecting an increase in local production in Jamaica which depended on an increased supply of input materials which may be sourced: (1) externally from overseas suppliers, (2) from post-consumer recycling, and (3) locally on the island of Jamaica. These three constructed scenarios were then compared to the existing supply chain or reference scenarios of the products. The results showed that for both case products the recycling scenario was most preferable for localising production, resulting in the lowest environmental impact. This was because the production of raw materials accounted for the largest effect on total environmental impact. As such, the most immediate environmental improvements were realised by lowering the production of virgin materials. © 2007 Elsevier Ltd. All rights reserved.

The production of separate streams of pure hydrogen and carbon dioxide from coal via an iron-oxide redox cycle

A chemical looping process using the redox reactions of iron oxide has been used to produce separate streams of pure H2 and CO2 from a solid fuel. An iron oxide carrier prepared using a mechanical mixing technique and comprised of 100wt.% Fe2O3 was used. It was demonstrated that hydrogen can be produced from three representative coals - a Russian bituminous, a German lignite and a UK sub-bituminous coal. Depending on the fuel, pure H2 with [CO] ≲50vol.ppm can be obtained from the proposed process. The cyclic stability of the iron oxide carrier was not adversely affected by contaminants found in syngas which are gaseous above 273K. Stable quantities of H2 were produced over five cycles for all three coals investigated. Independent of the fuel, SO2 was not formed during the oxidation with steam, i.e. the produced H2 was not contaminated with SO2. Since oxidation with air removes contaminants and generates useful heat and pure N2 for purging, it should be included in the operating cycle. Overall, it was demonstrated that the proposed process may be an attractive approach to upgrade crude syngas produced by the gasification of low-rank coals to pure H2, representing a substantial increase in calorific value, whilst simultaneous capturing CO2, a greenhouse gas. © 2010 Elsevier B.V.