Statistics of pathogenic bacteria in the search of host cells

Abstract

A crucial phase in the infection process, which remains poorly understood, is the localization of suitable host cells by bacteria. It is often assumed that chemotaxis plays a key role during this phase. Here, we report a quantitative study on how Salmonella Typhimurium search for T84 human colonic epithelial cells. Combining time-lapse microscopy and mathematical modeling, we show that bacteria can be described as chiral active particles with strong active speed fluctuations, which are of biological, as opposed to thermal, origin. We observe that there exists a giant range of inter-individual variability of the bacterial exploring capacity. Furthermore, we find Salmonella Typhimurium does not exhibit biased motion towards the cells and show that the search time statistics is consistent with a random search strategy. Our results indicate that in vitro localization of host cells, and also cell infection, are random processes, not involving chemotaxis, that strongly depend on bacterial motility parameters.

High-Definition DIC Imaging Uncovers Transient Stages of Pathogen Infection Cycles on the Surface of Human Adult Stem Cell-Derived Intestinal Epithelium

“…S2 A and C) but importantly did not allow simultaneous visualization of epithelial surface topology. These observations validate and extend previous studies of Salmonella motility ( 3 , 35 , 38 – 40 ) by mapping Salmonella NSS parameters atop a physiologically arranged epithelial surface and under minimally perturbing conditions.…”

High definition DIC imaging uncovers transient stages of pathogen infection cycles on the surface of human adult stem cell-derived intestinal epithelium

“…Reassessment of this pattern by fluorescence imaging resulted in broadly similar tracks (Fig S2A,C), but importantly did not allow simultaneous visualization of epithelial surface topology. These observations validate and extend previous studies of Salmonella motility (3, 33, 36–38), by mapping Salmonella NSS parameters atop a physiologically arranged epithelial surface and under minimally perturbing conditions.…”

Self-propulsion with speed and orientation fluctuation: exact computation of moments and dynamical bistabilities in displacement

“…At D v = 0, the expression for r 2 agrees with the results for ABPs in the absence of speed fluctuation [21]. Speed fluctuation enhances diffusivity, thereby rendering a mechanism for better spreading which might be utilized, e.g., by pathogenic bacteria in the search of host cells [35].…”

“…However, the mechanism of active speed generation itself is stochastic. For example, the speed distribution in the run and tumble motion of Myxobacteria is broad [32,33], and in the pathogenic E. coli, it displays a bimodality with peaks corresponding to run and stop [34,35]. This necessitates a description of ABP motion in the presence of speed fluctuations.…”