Researchers have made significant progress in understanding how a bacterial parasite can infect and multiply within the nuclei of deep-sea mussels found near hydrothermal vents and cold seeps. Their findings reveal that a single bacterial cell can invade the mussel’s nucleus and reproduce to form over 80,000 cells, all while keeping the host cell alive.
Many animals exist in close relationships with bacteria. A few of these bacteria are capable of living inside their host cells, but only a select few manage to survive within cell organelles (which are specialized structures within cells, similar to organs in a body). A unique group of bacteria has learned how to inhabit the nuclei of their host cells, which is particularly impressive since the nucleus serves as the command center of the cell.
Currently, there is limited knowledge about the specific molecular and cellular mechanisms employed by these bacteria that reside in the nuclei to infect and reproduce within animal hosts. Researchers from the Max Planck Institute for Marine Microbiology in Bremen, Germany, have now published the first detailed study on an intranuclear parasite in the journal Nature Microbiology.
How to reproduce in large numbers without damaging the host cell
This particular intranuclear parasite, known as Candidatus Endonucleobacter, targets the nuclei of deep-sea mussels located in hydrothermal vents and cold seeps across the globe. One bacterium can enter the mussel’s nucleus, where it swiftly reproduces into an astonishing 80,000 cells, leading to a swollen nucleus that expands to 50 times its normal size. Niko Leisch, co-senior author along with Nicole Dubilier from the Symbiosis Department at the Max Planck Institute for Marine Microbiology, explains, “We sought to understand how this bacterium infects and multiplies within nuclei and how it manages to obtain the necessary nutrients for its extensive reproduction without killing the host cell.”
The researchers employed various molecular and imaging techniques to show that Ca. Endonucleobacter feeds on sugars, lipids, and other cellular materials from the host, without breaking down its host’s nucleic acids, which is a common tactic among other intranuclear bacteria. This feeding method helps ensure the host cell continues to function long enough to supply the nutrients required for the bacterium’s impressive proliferation.
Power struggle for control over cell fate
Typically, when animal cells are infected, they may trigger apoptosis—a programmed cell death response. “Interestingly, these bacteria have devised a clever strategy to prevent their host cells from undergoing self-destruction,” says lead author Miguel Ángel González Porras. “They generate proteins known as inhibitors of apoptosis (IAPs) to suppress this process.” This sets off a competitive struggle: as the parasite produces more IAPs, the host cell responds by increasing its own production of proteins that promote apoptosis. Ultimately, once the parasite has effectively multiplied, the host cell bursts, releasing the bacteria to infect new cells.
Nicole Dubilier comments, “The discovery of IAPs in Ca. Endonucleobacter was one of the most unexpected findings of our research, as these proteins have only been recognized in animals and a few viruses but never identified in bacteria.” An analysis of the evolutionary lineage of IAPs indicates that the parasite likely acquired these genes from its host through a process known as horizontal gene transfer (HGT). While HGT from bacteria to eukaryotes is a well-established phenomenon, instances of HGT occurring in the reverse direction—as highlighted by the authors—are quite rare.
Impact on evolution and medicine
“Our findings deepen our understanding of the interactions between hosts and microbes and underscore the sophisticated survival strategies parasites have developed within their hosts,” notes Nicole Dubilier. These results may have far-reaching implications for studying parasitic infections and mechanisms of immune evasion in various organisms. “Our research illuminates a previously neglected mode of genetic exchange—HGT from eukaryotes to bacteria—that could change our perspective on microbial evolution and disease progression. Moreover, our study provides valuable insights into how apoptosis is regulated, which is significant for cancer research and cell biology,” concludes Niko Leisch.
