Fluid flow sensitizes bacterial pathogens to chemical stress

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Abstract
Cells regularly experience fluid flow in natural systems. However, most experimental systems rely on batch cell culture and fail to consider the effect of flow-driven dynamics on cell physiology. Using microfluidics and single-cell imaging, we discover that the interplay of physical shear rate (a measure of fluid flow) and chemical stress trigger a transcriptional response in the human pathogen Pseudomonas aeruginosa . In batch cell culture, cells protect themselves by quickly scavenging the ubiquitous chemical stressor hydrogen peroxide (H 2 O 2 ) from the media. In microfluidic conditions, we observe that cell scavenging generates spatial gradients of H 2 O 2 . High shear rates replenish H 2 O 2 , abolish gradients, and generate a stress response. Combining mathematical simulations and biophysical experiments, we find that cells in flow are sensitive to a H 2 O 2 concentration that is 100-1000 times lower than traditionally studied in batch cell culture. Surprisingly, the shear rate and H 2 O 2 concentration required to trigger a transcriptional response closely match their respective values in the human bloodstream. Thus, our results explain a long-standing discrepancy between H 2 O 2 levels in experimental and natural systems. Finally, we demonstrate that the shear rate and H 2 O 2 concentration found in the human bloodstream trigger gene expression in the blood-relevant human pathogen Staphylococcus aureus , suggesting that flow sensitizes bacteria to chemical stress in natural environments.

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