Biomedical subjects

N G Cogan

Publications and source records attributed to N G Cogan.

4 recordsLinked to original sources

PubMed2005

Effects of persister formation on bacterial response to dosing.

Almost all moist surfaces are colonized by microbial biofilms. Biofilms are implicated in cross-contamination of food products, biofouling and various human infections such as dental cavities, ulcerative colitis and chronic respiratory infections. The recalcitrance of biofilms to typical antibiotic and antimicrobial treatments is one focus of current investigations. Neither reaction-diffusion limitation nor heterogeneities in growth-rate explain the observed tolerance. Another hypothesis is that specialized 'persister' cells, which are extremely tolerant of antimicrobials, are the source of resistance. In this investigation, we describe the formation of 'persister' cells which neither grow nor die in the presence of antibiotics. We propose that these cells are of a different phenotype whose expression is regulated by the growth rate and the antibiotic concentration. Based on several experiments describing the dynamics of persister cells, we introduce a mathematical model that is used to describes the effect of a periodic dosing regiment. Results from our analysis indicate that the relative dose/withdrawal times are important in determining the effectiveness of such a treatment. A reduced model is also introduced and the similar behavior is demonstrated analytically.

Anti-Bacterial Agents↗

PubMed2005

Pattern formation by bacteria-driven flow.

Some marine bacterial species form mucosal layers, called veils, on sulfidic marine sediment. The bacteria attached to this veil actively swim and exert force on the surrounding fluid. The bacteria can break free of the veil and swim, chemotacting back to the veil. Over time the veil forms holes arranged in a hexagonal pattern. Motivated by this system, we present a simplified model to describe pattern formation induced by force-generating bodies embedded in a layer surrounded by fluid. When the bacteria break free of the layer, they are advected by the flow and diffuse. Competition between the fluid flow generated by the embedded bacteria and diffusion of the swimmers leads to a novel instability that drives bacterial aggregation. Analytic and numeric analysis of this system correctly defines the length scale and developmental timescale for the biological system. Similar flow dynamics may also play a role in other biological systems such as encrusting bryozoan colonies.

Bacterial Physiological Phenomena↗

PubMed2004

Modeling physiological resistance in bacterial biofilms.

A mathematical model of the action of antimicrobial agents on bacterial biofilms is presented. The model includes the fluid dynamics in and around the biofilm, advective and diffusive transport of two chemical constituents and the mechanism of physiological resistance. Although the mathematical model applies in three dimensions, we present two-dimensional simulations for arbitrary biofilm domains and various dosing strategies. The model allows the prediction of the spatial evolution of bacterial population and chemical constituents as well as different dosing strategies based on the fluid motion. We find that the interaction between the nutrient and the antimicrobial agent can reproduce survival curves which are comparable to other model predictions as well as experimental results. The model predicts that exposing the biofilm to low concentration doses of antimicrobial agent for longer time is more effective than short time dosing with high antimicrobial agent concentration. The effects of flow reversal and the roughness of the fluid/biofilm are also investigated. We find that reversing the flow increases the effectiveness of dosing. In addition, we show that overall survival decreases with increasing surface roughness.

Anti-Bacterial Agents↗

PubMed2004

The role of the biofilm matrix in structural development.

Although the initiation, development and control of biofilms has been an area of experimental investigation for more than three decades, the role of extra-cellular polymeric substance (EPS) has not been well studied. We present a mathematical description of the EPS matrix to study the development of heterogeneous biofilm morphology. In developing the model, we assume that the biofilm is a biological gel composed of EPS and water. The bacteria are enmeshed in the network and are the producers of the polymer. In response to external conditions, gels absorb or expel solvent causing swelling or contraction due to osmotic pressure gradients. The physical morphology of the biofilm depends on the temperature, solvent composition, pH and ionic concentrations through osmotic pressure. This gives a physically based mechanism for the redistribution of biomass within the biofilm. Analysis of a reduced model indicates that biomass redistribution, through the mechanism of swelling, may induce the formation of isolated towers or mushroom clusters by spatial variation in EPS production which leads to gradients in osmotic pressure.

Biofilms↗