Host-induced spermidine production in motile Pseudomonas aeruginosa triggers phagocytic uptake

Exploring the complexity of host-pathogen communication is vital to understand why microbes persist within a host, while others are cleared. Here, we employed a Dual-sequencing approach to unravel conversational turn-taking of dynamic host-pathogen communications. We demonstrate that upon hitting a host cell, motile Pseudomonas aeruginosa induce a specific gene expression program. This results in the expression of spermidine on the surface, which specifically activates the PIP3-pathway to induce phagocytic uptake into primary or immortalized murine cells. Non-motile bacteria are more immunogenic due to a lower expression of arnT upon host cell contact, but do not produce spermidine and are phagocytosed less. We demonstrate that not only the presence of pathogen inherent molecular patterns induces immune responses, but that bacterial motility is linked to a host-cell induced expression of additional immune modulators. Our results emphasize on the value of integrating microbiological and immunological findings to unravel complex and dynamic host-pathogen interactions. Overall design: DualSeq (RNASeq) of RAW264.7 macrophages infected with Pseudomonas aeruginosa PA14 wild-type and different motility mutants. RNASeq of Pseudomonas aeruginosa PA14 wild-type and different motility mutants - planctonic growth in LB medium. RNASeq of RAW264.7 macrophages treated with spermidine.