Mechanosensation induces persistent bacterial growth during bacteriophage predation

Abstract

ABSTRACT Although the relationship between bacteria and lytic bacteriophage is fundamentally antagonistic, these microbes not only coexist but thrive side by side in myriad ecological environments. The mechanisms by which coexistence is achieved, however, are not fully understood. By examining Escherichia coli and bacteriophage T7 population dynamics at the single-cell and single-virion level using a novel microfluidics assay, we observed bacteria growing “persistently” when perfused with high-titer bacteriophage. Bacteriophage persistence occurred at a frequency five orders of magnitude higher than is expected from the natural selection of bacteriophage-resistant mutants. Rather, the frequency of persistence was correlated with the degree to which the bacteria were mechanically compressed by the microfluidic perfusion chamber. Using a combination of mutagenesis and fluorescent imaging techniques, we discovered that compression induces persistence by activating the Rcs phosphorelay pathway, which results in the synthesis of extracellular capsule that sterically blocks bacteriophage adsorption. Other forms of mechanical perturbation also promoted Rcs activity and persistence. These findings have important implications for our understanding of microbial ecology in many important environments, including the gut and the soil, where bacteria grow in confinement. IMPORTANCE Bacteria and bacteriophage form one of the most important predator-prey relationships on earth, yet how the long-term stability of this ecological interaction is achieved is unclear. Here, we demonstrate that Escherichia coli can rapidly grow during bacteriophage predation if they are doing so in spatially confined environments. This discovery revises our understanding of bacteria-bacteriophage population dynamics in many real-world environments where bacteria grow in confinement, such as the gut and the soil. Additionally, this result has clear implications for the potential of bacteriophage therapy and the role of mechanosensation during bacterial pathogenesis.