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.

Industrial ecology at factory level - A conceptual model

Growing environmental concerns caused by natural resource depletion and pollution need to be addressed. One approach to these problems is Sustainable Development, a key concept for our society to meet present as well as future needs worldwide. Manufacturing clearly has a major role to play in the move towards a more sustainable society. However it appears that basic principles of environmental sustainability are not systematically applied, with practice tending to focus on local improvements. The aim of the work presented in this paper is to adopt a more holistic view of the factory unit to enable opportunities for wider improvement. This research analyses environmental principles and industrial practice to develop a conceptual manufacturing ecosystem model as a foundation to improve environmental performance. The model developed focuses on material, energy and waste flows to better understand the interactions between manufacturing operations, supporting facilities and surrounding buildings. The research was conducted in three steps: (1) existing concepts and models for industrial sustainability were reviewed and environmental practices in manufacturing were collected and analysed; (2) gaps in knowledge and practice were identified; (3) the outcome is a manufacturing ecosystem model based on industrial ecology (IE). This conceptual model has novelty in detailing IE application at factory level and integrating all resource flows. The work is a base on which to build quantitative modelling tools to seek integrated solutions for lower resource input, higher resource productivity, fewer wastes and emissions, and lower operating cost within the boundary of a factory unit. © 2012 Elsevier Ltd. All rights reserved.

Industrial ecology at factory level: A prototype methodology

The concept of sustainable manufacturing is a form of pollution prevention that integrates environmental considerations in the production of goods while focusing on efficient resource use. Taking the industrial ecology perspective, this efficiency comes from improved resource flow management. The assessment of material, energy and waste resource flows, therefore, offers a route to viewing and analysing a manufacturing system as an ecosystem using industrial ecology biological analogy and can, in turn, support the identification of improvement opportunities in the material, energy and waste flows. This application of industrial ecology at factory level is absent from the literature. This article provides a prototype methodology to apply the concepts of industrial ecology using material, energy and waste process flows to address this gap in the literature. Various modelling techniques were reviewed and candidates selected to test the prototype methodology in an industrial case. The application of the prototype methodology showed the possibility of using the material, energy and waste resource flows through the factory to link manufacturing operations and supporting facilities, and to identify potential improvements in resource use. The outcomes of the work provide a basis to build the specifications for a modelling tool that can support those analysing their manufacturing system to improve their environmental performance and move towards sustainable manufacturing. © IMechE 2012.