Male-killing symbiont damages host's dosage-compensated sex chromosome to induce embryonic apoptosis.

Male-killing symbiont damages host's dosage-compensated sex chromosome to induce embryonic apoptosis.
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DOI:
10.1038/ncomms12781
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发表时间:
2016-09-21
影响因子:
16.6
通讯作者:
Fukatsu T
Fukatsu T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Harumoto T;Anbutsu H;Lemaitre B;Fukatsu T

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一些共生细菌能够以自私的方式干扰宿主的繁殖。这些细菌如何操纵宿主的性别相关机制是细胞、发育和进化生物学的根本兴趣所在。在这里,我们揭示了螺旋体诱导果蝇胚胎雄性致死的分子和细胞机制。转录分析表明,许多与DNA损伤和细胞凋亡相关的基因在感染的男性胚胎中特异上调。详细的遗传学和细胞学分析表明,杀死男性的螺旋体与男性特异性致死(MSL)复合体相互作用,导致男性X染色体上的DNA损伤。在有丝分裂过程中,受损的男性X染色体呈现染色质桥,桥的断裂通过P53依赖的途径触发性别特异性的异常凋亡。值得注意的是,MSL复合体不仅对于这种细胞毒过程是必要的,而且也是充分的。这些结果突显了共生生物针对宿主性染色体的复杂策略,并以性别特有的方式招募宿主的分子级联,导致大量细胞凋亡。共生细菌能够以对宿主有机体有害的方式干扰宿主的繁殖。在这里,作者表明,螺旋体诱导果蝇雄性X染色体上的DNA损伤,导致性别特异性的细胞凋亡。
Some symbiotic bacteria are capable of interfering with host reproduction in selfish ways. How such bacteria can manipulate host's sex-related mechanisms is of fundamental interest encompassing cell, developmental and evolutionary biology. Here, we uncover the molecular and cellular mechanisms underlying Spiroplasma-induced embryonic male lethality in Drosophila melanogaster. Transcriptomic analysis reveals that many genes related to DNA damage and apoptosis are up-regulated specifically in infected male embryos. Detailed genetic and cytological analyses demonstrate that male-killing Spiroplasma causes DNA damage on the male X chromosome interacting with the male-specific lethal (MSL) complex. The damaged male X chromosome exhibits a chromatin bridge during mitosis, and bridge breakage triggers sex-specific abnormal apoptosis via p53-dependent pathways. Notably, the MSL complex is not only necessary but also sufficient for this cytotoxic process. These results highlight symbiont's sophisticated strategy to target host's sex chromosome and recruit host's molecular cascades toward massive apoptosis in a sex-specific manner. Symbiotic bacteria are able to interfere with host reproduction in ways that are detrimental to the host organism. Here the authors show that Spiroplasma induces DNA damage on the male X chromosome in Drosophila, causing sex-specific apoptosis.