Bugs on a Slippery Plane : Understanding the Motility of Microbial Pathogens with Mathematical Modelling

Many pathogenic microorganisms live in close association with surfaces, typically in thin films that either arise naturally or that they themselves create. In response to this constrained environment, the cells adjust their behaviour and morphology, invoking communication channels and inducing physical phenomena that allow for rapid colonization of biomedically relevant surfaces or the promotion of virulence factors. Thus, it is very important to measure and theoretically understand the key mechanisms for the apparent advantage obtained from swimming in thin films. We discuss experimental measurements of flows around a peritrichously flagellated bacterium constrained in a thin film, derive a simplified mathematical theory and Green's functions for flows in a thin film with general slip boundary conditions, and establish connections between theoretical and experimental results. This article aims to highlight the importance of mathematics as a tool to unlock qualitative mechanisms associated with experimental observations in the medical and biological sciences

Gyrotactic swimmer dispersion in pipe flow: testing the theory

Suspensions of microswimmers are a rich source of fascinating new fluid mechanics. Recently we predicted the active pipe flow dispersion of gyrotactic microalgae, whose orientation is biased by gravity and flow shear. Analytical theory predicts that these active swimmers disperse in a markedly distinct manner from passive tracers (Taylor dispersion). Dispersing swimmers display non-zero drift and effective diffusivity that is non-monotonic with Péclet number. Such predictions agree with numerical simulations, but hitherto have not been tested experimentally. Here, to facilitate comparison, we obtain new solutions of the axial dispersion theory accounting both for swimmer negative buoyancy and a local nonlinear response of swimmers to shear, provided by two alternative microscopic stochastic descriptions. We obtain new predictions for suspensions of the model swimming alga Dunaliella salina, whose motility and buoyant mass we parametrise using tracking video microscopy. We then present a new experimental method to measure gyrotactic dispersion using fluorescently stained D. salina and provide a preliminary comparison with predictions of a non-zero drift above the mean flow for each microscopic stochastic description. Finally, we propose further experiments for a full experimental characterisation of gyrotactic dispersion measures and discuss the implications of our results for algal dispersion in industrial photobioreactors

Quorum machinery : Effect of the las system in rhl regulation of P. aeruginosa

Quorum sensing (QS) describes a communication mechanism via signal molecules that allows colonies of bacteria to coordinate gene expression. The nature of the QS system depends very much on the species. Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that has a highly complex QS system. The QS signalling system of P. aeruginosa is known to involve multiple control components, notably las, rhl and pqs systems. The QS signalling system of P. aeruginosa is responsive to two chemically different signal molecules, based on Homoserine-Lactones (HSLs) and 4-quinilines (4Qs). This paper focuses on the relation of the first two systems that manage Homoserine-Lactone (HSL) production since this is the main chemical signalling in P. aeruginosa that regulates many activities of bacteria, including symbiosis, virulence factors, motility, production of antibiotics, and formation of biofilm. The las and rhl system of P. aeruginosa do not act independently. Some gene expression that is regulated by rhl system is also controlled by the las system. Previous research has demonstrated that the las system can give rise to excitable pulse generation of signal molecule production. This paper examines the mechanism of how las and rhl systems act in tandem to generate sophisticated control on QS system of P. aeruginosa. Using analytic methods, it is shown how dynamics of the rhl system is affected by dynamics of the las system

A discrete slug population model determined by egg production

Slugs are significant pests in agriculture (as well as a nuisance to gardeners), and it is therefore important to understand their population dynamics for the construction of efficient and effective control measures. Differential equation models of slug populations require the inclusion of large (variable) temporal delays, and strong seasonal forcing results in a non-autonomous system. This renders such models open to only a limited amount of rigorous analysis. In this paper, we derive a novel batch model based purely upon the quantity of eggs produced at different times of the year. This model is open to considerable reduction; from the resulting two variable discrete-time system it is possible to reconstruct the dynamics of the full population across the year and give conditions for extinction or global stability and persistence. Furthermore, the steady state temporal population distribution displays qualitatively different behavior with only small changes in the survival probability of slugs. The model demonstrates how small variations in the favorability of different years may result in widely different slug population fluctuations between consecutive years, and is in good agreement with field data

Dispersion of swimming algae in laminar and turbulent channel flows: consequences for photobioreactors

Shear flow significantly affects the transport of swimming algae in suspension. For example, viscous and gravitational torques bias bottom-heavy cells to swim towards regions of downwelling fluid (gyrotaxis). It is necessary to understand how such biases affect algal dispersion in natural and industrial flows, especially in view of growing interest in algal photobioreactors. Motivated by this, we here study the dispersion of gyrotactic algae in laminar and turbulent channel flows using direct numerical simulation (DNS) and the analytical swimming dispersion theory of Bees and Croze (2010). Time-resolved dispersion measures are evaluated as functions of the Peclet and Reynolds numbers in upwelling and downwelling flows. For laminar flows, DNS results are compared with theory using competing descriptions of biased swimming cells in shear flow. Excellent agreement is found for predictions that employ generalized-Taylor-dispersion. The results highlight peculiarities of gyrotactic swimmer dispersion relative to passive tracers. In laminar downwelling flow the cell distribution drifts in excess of the mean flow, increasing in magnitude with Peclet number. The cell effective axial diffusivity increases and decreases with Peclet number (for tracers it merely increases). In turbulent flows, gyrotactic effects are weaker, but discernable and manifested as non-zero drift. These results should significantly impact photobioreactor design.Comment: 31 pages, 15 figures (includes supplementary materials

Microbial mutualism at a distance: The role of geometry in diffusive exchanges

The exchange of diffusive metabolites is known to control the spatial patterns formed by microbial populations, as revealed by recent studies in the laboratory. However, the matrices used, such as agarose pads, lack the structured geometry of many natural microbial habitats, including in the soil or on the surfaces of plants or animals. Here we address the important question of how such geometry may control diffusive exchanges and microbial interaction. We model mathematically mutualistic interactions within a minimal unit of structure: two growing reservoirs linked by a diffusive channel through which metabolites are exchanged. The model is applied to study a synthetic mutualism, experimentally parametrized on a model algal-bacterial co-culture. Analytical and numerical solutions of the model predict conditions for the successful establishment of remote mutualisms, and how this depends, often counterintuitively, on diffusion geometry. We connect our findings to understanding complex behavior in synthetic and naturally occurring microbial communities.Gates Cambridge Trust The Winton Foundation for the Physics of Sustainability The Royal Society The Schlumberger Chair Fun

Emergent features due to grid-cell biology: synchronisation in biophysical models

Modelling studies of upper ocean phenomena, such as that of the spatial and temporal patchiness in plankton distributions, typically employ coupled biophysical models, with biology in each grid-cell represented by a plankton ecosystem model. It has not generally been considered what impact the choice of grid-cell ecosystem model, from the many developed in the literature, might have upon the results of such a study. We use the methods of synchronisation theory, which is concerned with ensembles of interacting oscillators, to address this question, considering the simplest possible case of a chain of identically represented interacting plankton grid-cells. It is shown that the ability of the system to exhibit stably homogeneous (fully synchronised) dynamics depends crucially upon the choice of biological model and number of grid-cells, with dynamics changing dramatically at a threshold strength of mixing between grid-cells. Consequently, for modelling studies of the ocean the resolution chosen, and therefore number of grid-cells used, could drastically alter the emergent features of the model. It is shown that chaotic ecosystem dynamics, in particular, should be used with care

Differential dynamic microscopy: a high-throughput method for characterizing the motility of microorganisms

We present a fast, high-throughput method for characterizing the motility of microorganisms in three dimensions based on standard imaging microscopy. Instead of tracking individual cells, we analyze the spatiotemporal fluctuations of the intensity in the sample from time-lapse images and obtain the intermediate scattering function of the system. We demonstrate our method on two different types of microorganisms: the bacterium Escherichia coli (both smooth swimming and wild type) and the biflagellate alga Chlamydomonas reinhardtii. We validate the methodology using computer simulations and particle tracking. From the intermediate scattering function, we are able to extract the swimming speed distribution, fraction of motile cells, and diffusivity for E. coli, and the swimming speed distribution, and amplitude and frequency of the oscillatory dynamics for C. reinhardtii. In both cases, the motility parameters were averaged over ∼410 cells and obtained in a few minutes