Most animals live in intimate relationships with bacteria. Some of these bacteria live in the cells of their hosts, but very few can live in cell organelles (structures within the cell, such as organs in the body). One group of bacteria has discovered how to colonize the nuclei of their hosts, a remarkable achievement considering that the nucleus is the cell’s control center.
To date, nothing is known about the molecular and cellular processes these intranuclear bacteria use to infect and reproduce in animal hosts. A group of scientists from the Max Planck Institute for Marine Microbiology in Bremen, Germany, now present the first in-depth analysis of an intranuclear parasite of animals in a study published in Natural microbiology.
How to reproduce en masse in a cell without killing it
This intranuclear parasite, Candidatus Endonucleobacter infects the cores of deep-sea mussels from hydrothermal vents and cold seeps across the globe. A single bacterial cell invades the mussel’s nucleus and then reproduces into more than 80,000 cells, causing the nucleus to swell to 50 times its original size. “We wanted to understand how the bacteria infect and reproduce in nuclei, and in particular how these bacteria obtain the nutrients they need for their massive replication, yet prevent their host cells from dying,” said Niko Leisch, co-senior author together with Nicole. Dubilier from the Symbiosis Department of the Max Planck Institute for Marine Microbiology.
Using a series of molecular and imaging methods, the scientists revealed that Approx. Endonucleobacter lives on sugars, lipids and other cell components of its host. It does not digest its host nucleic acids like many other intranuclear bacteria. This nutritional strategy ensures that the host cell functions long enough to provide Approx. Endonucleobacter with the nutrients it needs to multiply in such enormous numbers.
Arms race for control of the cell
A common response of animal cells to infection is apoptosis – a suicide program that cells initiate when damaged or infected by bacteria or viruses. “Interestingly, these bacteria have devised a sophisticated strategy to prevent their host cells from killing themselves,” says first author Miguel Ángel González Porras. “They produce proteins that suppress apoptosis, called inhibitors of apoptosis (IAPs).” An arms race then ensues to control cell death: as the bacteria produce more and more IAPs, the host cell increases the production of proteins that cause apoptosis. Eventually, after the parasite has had sufficient time to multiply en masse, the host cell ruptures, releasing the bacteria and allowing new host cells to be infected.
Nicole Dubilier adds: “The discovery of IAPs in Approx. Endonucleobacter was one of the most surprising results of our study, because these proteins are only known from animals and a few viruses, but have never been found in bacteria. acquired these genes from its host via horizontal gene transfer (HGT). Although HGT from bacteria to eukaryotes is well known, very few examples of HGT in the opposite direction are known – as the authors have now discovered.
Implications from evolution to medicine
“Our discovery advances our understanding of host-microbe interactions and highlights the complex strategies that parasites have evolved to thrive in their hosts,” explains Nicole Dubilier. These findings may have broader implications for studying parasitic infections and immune evasion strategies in other organisms. “Our research sheds light on an overlooked mechanism of genetic exchange – HGT from eukaryotes to bacteria – that could potentially impact the way we understand microbial evolution and pathogenesis. Furthermore, our study provides insight into the regulation of apoptosis , which is relevant for cancer research and cell biology,” concludes Niko Leisch.
