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.

Can frequency diversity provide performance gains for WSNs at 2.4GHz for the fire hydrant to above ground channel

Wireless Sensor Networks (WSNs) which utilise IEEE 802.15.4 technology offer the potential for low cost deployment and maintenance compared with conventional wired sensor networks, enabling effective and efficient condition monitoring of aged civil engineering infrastructure. We will address wireless propagation for a below to above ground scenario where one of the wireless nodes is located in a below ground fire hydrant chamber to permit monitoring of the local water distribution network. Frequency Diversity (FD) is one method that can be used to combat the damaging effects of multipath fading and so improve the reliability of radio links. However, no quantitative investigation concerning the potential performance gains from the use of FD at 2.4GHz is available for the outlined scenario. In this paper, we try to answer this question by performing accurate propagation measurements using modified and calibrated off-the-shelf 802.15.4 based sensor nodes. These measurement results are also compared with those obtained from simulations that employ our Modified 2D Finite-Difference Time-Domain (FDTD) approach. ©2009 IEEE.

Frequency diversity measurements at 2.4 GHz for wireless sensor networks deployed in tunnels

Wireless Sensor Networks (WSNs) which utilise IEEE 802.15.4 technology operate primarily in the 2.4 GHz globally compatible ISM band. However, the wireless propagation channel in this crowded band is notoriously variable and unpredictable, and it has a significant impact on the coverage range and quality of the radio links between the wireless nodes. Therefore, the use of Frequency Diversity (FD) has potential to ameliorate this situation. In this paper, the possible benefits of using FD in a tunnel environment have been quantified by performing accurate propagation measurements using modified and calibrated off-the-shelf 802.15.4 based sensor motes in the disused Aldwych underground railway tunnel. The objective of this investigation is to characterise the performance of FD in this confined environment. Cross correlation coefficients are calculated from samples of the received power on a number of frequency channels gathered during the field measurements. The low measured values of the cross correlation coefficients indicate that applying FD at 2.4 GHz will improve link performance in a WSN deployed in a tunnel. This finding closely matches results obtained by running a computational simulation of the tunnel radio propagation using a 2D Finite-Difference Time-Domain (FDTD) method. ©2009 IEEE.

Probing biomolecular interaction forces using an anharmonic acoustic technique for selective detection of bacterial spores.

Receptor-based detection of pathogens often suffers from non-specific interactions, and as most detection techniques cannot distinguish between affinities of interactions, false positive responses remain a plaguing reality. Here, we report an anharmonic acoustic based method of detection that addresses the inherent weakness of current ligand dependant assays. Spores of Bacillus subtilis (Bacillus anthracis simulant) were immobilized on a thickness-shear mode AT-cut quartz crystal functionalized with anti-spore antibody and the sensor was driven by a pure sinusoidal oscillation at increasing amplitude. Biomolecular interaction forces between the coupled spores and the accelerating surface caused a nonlinear modulation of the acoustic response of the crystal. In particular, the deviation in the third harmonic of the transduced electrical response versus oscillation amplitude of the sensor (signal) was found to be significant. Signals from the specifically-bound spores were clearly distinguishable in shape from those of the physisorbed streptavidin-coated polystyrene microbeads. The analytical model presented here enables estimation of the biomolecular interaction forces from the measured response. Thus, probing biomolecular interaction forces using the described technique can quantitatively detect pathogens and distinguish specific from non-specific interactions, with potential applicability to rapid point-of-care detection. This also serves as a potential tool for rapid force-spectroscopy, affinity-based biomolecular screening and mapping of molecular interaction networks.