Interkingdom signaling molecule leads to genomic instability in Emiliania huxleyi causing cell cycle arrest without mortality: Do bacteria use chemical signals to exploit eukaryotic cells?

In the ocean, bacteria and phytoplankton play a central role in driving oceanic biogeochemical cycling. Often the interactions among these microbes are chemically mediated, yet, the mechanisms that underlie these chemical communications are often not well understood. Here, we discuss the mechanisms that promote the static growth of the coccolithophore, Emiliania huxleyi upon exposure to nanomolar concentrations of the bacteria signaling molecule, 2-heptyl-4-quinolone (HHQ). Transcriptomic and proteomic analyses interrogating the molecular impacts of HHQ on E. huxleyi physiology highlight significant upregulation of DNA damage repair (DDR) and energy production pathways. Of note was the significant upregulation of genes within the poly(ADP-ribose) (PARP) family, an enzyme required for genomic stability. PARP proteins have yet to be characterized in phytoplankton, however, they orchestrate and catalyze DNA replication and the DDR response in mammalian cells. In HHQ-exposed E. huxleyi cells, DNA replication is halted suggesting this fundamental pathway may be compromised. We determined that HHQ has an inhibitory effect against mammalian PARPs, and E. huxleyi PARPs share a highly conserved catalytic domain with human PARPs. Meanwhile, other phytoplankton species that lack PARP homologs are fully resistant to HHQ. In addition, various viruses are known to control PARP activity during infection and require the host’s DNA replication machinery to propagate, leading us to postulate that the PARP enzyme maybe an intercellular target of HHQ in eukaryotic phytoplankton and in turn affect viral replication. Preliminary data suggesting that HHQ exposure may ameliorate viral-induced mortality supports this hypothesis. These results reveal a chemically-mediated mechanism by which a heterotrophic bacterium may be able to hijack the molecular machinery of a phytoplankton cell, influencing population dynamics and, ultimately, biogeochemical cycling in the ocean.