Mechanosensation 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 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.

Integrative gene network analysis identifies key signatures, intrinsic networks and host factors for influenza virus A infections.

Influenza A virus, with the limited coding capacity of 10-14 proteins, requires the host cellular machinery for many aspects of its life cycle. Knowledge of these host cell requirements not only reveals molecular pathways exploited by the virus or triggered by the immune system, but also provides further targets for antiviral drug development. To uncover novel pathways and key targets of influenza infection, we assembled a large amount of data from 12 cell-based gene-expression studies of influenza infection for an integrative network analysis. We systematically identified differentially expressed genes and gene co-expression networks induced by influenza infection. We revealed the dedicator of cytokinesis 5 (DOCK5) played potentially an important role for influenza virus replication. CRISPR/Cas9 knockout of DOCK5 reduced influenza virus replication, indicating that DOCK5 is a key regulator for the viral life cycle. DOCK5's targets determined by the DOCK5 knockout experiments strongly validated the predicted gene signatures and networks. This study systematically uncovered and validated fundamental patterns of molecular responses, intrinsic structures of gene co-regulation, and novel key targets in influenza virus infection.