Mechanical compression induces persistent bacterial growth during bacteriophage predation

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-based assay, we observed bacteria growing “persistently” when perfused with high-titer bacteriophage. Persistence occurred at a frequency five orders of magnitude higher than is expected from 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 found 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 stimulation 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.