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.

Transposon mutagenesis in a hyper-invasive clinical isolate of Campylobacter jejuni reveals a number of genes with potential roles in invasion.

Transposon mutagenesis has been applied to a hyper-invasive clinical isolate of Campylobacter jejuni, 01/51. A random transposon mutant library was screened in an in vitro assay of invasion and 26 mutants with a significant reduction in invasion were identified. Given that the invasion potential of C. jejuni is relatively poor compared to other enteric pathogens, the use of a hyper-invasive strain was advantageous as it greatly facilitated the identification of mutants with reduced invasion. The location of the transposon insertion in 23 of these mutants has been determined; all but three of the insertions are in genes also present in the genome-sequenced strain NCTC 11168. Eight of the mutants contain transposon insertions in one region of the genome (approximately 14 kb), which when compared with the genome of NCTC 11168 overlaps with one of the previously reported plasticity regions and is likely to be involved in genomic variation between strains. Further characterization of one of the mutants within this region has identified a gene that might be involved in adhesion to host cells.

Make or buy decision in the context of manufacturing strategy

This paper describes an approach to structuring the make or buy decision process, basing it firmly in the context of an overall manufacturing strategy. The work has been carried out jointly by the University of Cambridge Manufacturing Engineering Group and Lucas Industries. A review of the current state of ideas surrounding the linked issues of vertical integration and make or buy decisions is presented. Important features of the approach include identification of core manufacturing capabilities, assessment of the role of technology in manufacturing, the development of a cost model to support make or buy decisions and a review of the strategic implications of varying degrees of vertical integration.

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.