The Pseudomonas aeruginosa autoinducer dodecanoyl-homoserine lactone inhibits the putrescine synthesis in human cells

Pseudomonas aeruginosa uses acyl-homoserine lactones to coordinate gene transcription in a process called quorum sensing (QS). The QS molecules C-4-HSL and C-12-oxo-HSL are synthesized from the universal precursor S-adenosyl methionine, which is also a precursor of polyamines in human cells. Polyamines are required for mitotic cell division and peak during this phase. The polyamine putrescine is synthesized by ornithine decarboxylase (ODC) as a rate-limiting step. The ODC enzyme concentration also peaks during the mitotic phase. This peak is mediated by translation of ODC mRNA by the ITAF45 protein, which translocates from the nuclear compartment to the cytoplasm in a phosphorylation-dependent manner. We observed that C-12-HSL-treated human epidermal cells had a higher cytoplasm-to-nuclear ITAF45 protein concentration and this translocation was dependent on the dephosphorylation of ITAF45. Finally, C-12-HSL-treated cells also had a time-course-dependent higher concentration of ODC mRNA. Based on these mitotic markers, more human cells were apparently trapped in the mitotic phase when treated with C-12-HSL. This should normally imply higher levels of putrescine. However, C-12-HSL-treated human cells had a significantly lower concentration of putrescine and displayed a lower cell proliferation rate. In conclusion, the P. aeruginosa autoinducer C-12-oxo-HSL apparently arrests human cells in the mitotic phase by lowering the concentration of putrescine.