An intranuclear bacterial parasite of deep-sea mussels expresses apoptosis inhibitors acquired from its host

Only a few bacteria are able to colonize the nuclei of eukaryotes and nearly all of these are known from protists. One bacterial clade, however, “Candidatus Endonucleobacter”, infects the nuclei of deep-sea mussels, where it replicates to ≥ 80,000 bacteria per nucleus and causes nuclei to swell to 50 times their original size. How these parasites are able to replicate so massively and avoid apoptosis is not known. Dual RNA-seq transcriptomes of infected nuclei isolated using laser-capture microdissection revealed that in contrast to previous assumptions, “Ca. Endonucleobacter” does not gain most of its nutrition from nuclear DNA or RNA. Instead, “Ca. Endonucleobacter” upregulated genes for importing sugars, lipids, amino acids and possibly mucin from its host, and digested these nutrients. “Ca. Endonucleobacter” likely prevents apoptosis of host cells by upregulating 7-13 inhibitors of apoptosis (IAPs), proteins previously only known from animals and a few invertebrate viruses. Comparative phylogenetic analyses revealed that “Ca. Endonucleobacter” acquired IAPs repeatedly through horizontal gene transfer (HGT) from their hosts in convergent acquisition. HGT from eukaryotes to bacteria, although assumed to be rare, may be more common than currently recognized, particularly in bacteria that live in intimate associations with eukaryotic hosts.

仅有极少数细菌能够定殖于真核生物的细胞核中，且目前已知的此类细菌几乎全部来自原生生物（protists）。然而，其中一个细菌演化支——候选命名类群"Candidatus Endonucleobacter"——可侵染深海贻贝的细胞核，每个细胞核内其菌体可增殖至80000个以上，并使细胞核膨大至原始体积的50倍。目前尚不清楚这类寄生虫为何能实现如此大规模的增殖，且能规避宿主细胞凋亡（apoptosis）。研究人员通过激光捕获显微切割（laser-capture microdissection）分离受侵染的细胞核，并对其开展双RNA测序（dual RNA-seq）转录组分析，结果显示，与此前的推测相悖，"Ca. Endonucleobacter"的大部分营养并非来自宿主细胞核的DNA或RNA。相反，"Ca. Endonucleobacter"上调了负责从宿主摄取糖类、脂质、氨基酸以及可能存在的黏蛋白（mucin）的相关基因，并对这些营养物质进行消化利用。"Ca. Endonucleobacter"大概率通过上调7~13个细胞凋亡抑制因子（inhibitors of apoptosis, IAPs）的表达，来阻止宿主细胞发生凋亡；这类蛋白此前仅在动物及少数无脊椎动物病毒中被发现。比较系统发育分析结果表明，"Ca. Endonucleobacter"通过反复的水平基因转移（horizontal gene transfer, HGT）从宿主处趋同获得了IAPs基因。尽管此前认为真核生物向细菌的水平基因转移事件较为罕见，但这类事件的发生频率或许比目前认知的更高，尤其是在与真核宿主形成紧密共生关系的细菌类群中。