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Many organisms establish close relationships with bacteria, with some of these microorganisms managing to inhabit the cells of their hosts. However, only a limited number of bacteria have the capability to reside within specific organelles, such as the nucleus, which serves as the cell’s command center. A particular group of bacteria has adapted to colonize the nuclei, showcasing an extraordinary survival strategy.
Recent research conducted by scientists at the Max Planck Institute for Marine Microbiology in Bremen, Germany, has shed light on these intranuclear bacteria, marking the first comprehensive investigation of a parasitic species within animal nuclei. The findings are detailed in a publication in Nature Microbiology.
Reproducing on a grand scale without harming the host
The bacterial species in question, Candidatus Endonucleobacter, targets the nuclei of deep-sea mussels found around hydrothermal vents and cold seeps globally. Remarkably, a single bacterium can proliferate into over 80,000 cells, expanding the nucleus to an astonishing 50 times its original volume. “Our aim was to decipher the infection and reproduction mechanisms of this bacterium within the nucleus, especially how it secures nutrients for such extensive replication while keeping the host cell viable,” explains Niko Leisch, one of the study’s co-senior authors, along with Nicole Dubilier from the institute’s Symbiosis Department.
The researchers employed various molecular and imaging techniques, discovering that Ca. Endonucleobacter thrives on sugars, lipids, and other materials derived from its host. Interestingly, unlike many other intranuclear bacteria, it does not break down the host’s nucleic acids. This nutritional strategy allows the host cell to maintain functionality long enough to provide the essential resources required for such prolific bacterial reproduction.
A battle for cellular dominance
Typically, when faced with infection, animal cells may trigger apoptosis, a self-destruct mechanism activated when they detect damage or infection. “What’s fascinating is how these bacteria have developed a complex approach to inhibit host cell apoptosis,” remarks Miguel Ángel González Porras, the study’s first author. “They produce proteins known as inhibitors of apoptosis (IAPs) that help to prevent the host cells from undergoing programmed cell death.” This initiation results in a cellular tug-of-war: as the bacteria increase the production of IAPs, the host escalates the generation of proteins that promote apoptosis. In time, after sufficient bacterial replication, the host cell ultimately bursts, allowing the bacteria to escape and invade additional cells.
Nicole Dubilier notes, “The finding of IAPs within Ca. Endonucleobacter was particularly unexpected, as these proteins have previously only been identified in animals and select viruses, not in bacteria.” Investigations into the evolutionary connections of these IAPs suggest that the bacteria likely obtained these genes from their host via horizontal gene transfer (HGT). Although HGT from bacteria to eukaryotes is a well-documented phenomenon, instances of HGT occurring in the reverse direction are exceptionally rare.
Broader implications for evolution and health
“This discovery broadens our comprehension of host-microbe interactions and underscores the intricate strategies evolved by parasites to flourish within their hosts,” states Nicole Dubilier. The implications of these findings may extend to parasitic infections and immune evasion tactics in various organisms. “Our research illuminates a previously underappreciated mechanism of genetic exchange—HGT from eukaryotes to bacteria—potentially reshaping our understanding of microbial evolution and pathogenesis. Additionally, our study provides valuable insights into the regulation of apoptosis, which carries significance for cancer research and cell biology,” concludes Niko Leisch.
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