title: Male-killing symbiont damages host's dosage-compensated sex chromosome to induce embryonic apoptosis.
abstract: 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.
authors.affiliation: Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566, Japan.|Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, Switzerland.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Harumoto
authors.affiliation: Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Anbutsu
authors.affiliation: Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Station 19, CH-1015 Lausanne, Switzerland.
authors.forename: Bruno
authors.identifier: 0000-0001-7970-1667
authors.initials: B
authors.lastname: Lemaitre
authors.affiliation: Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566, Japan.
authors.forename: Takema
authors.identifier: 0000-0001-5987-2602
authors.initials: T
authors.lastname: Fukatsu
mesh_terms: D000818:Animals; D017209:Apoptosis; D004331:Drosophila melanogaster / Q000196:embryology / Q000382:microbiology*; D004625:Embryo, Nonmammalian / Q000382:microbiology*; D005260:Female; D054884:Host-Pathogen Interactions; D008297:Male; D013149:Spiroplasma / Q000502:physiology*