Perplexing dynamics of Wolbachia proteins for cytoplasmic incompatibility

The mechanism of symbiont-induced cytoplasmic incompatibility (CI) has been a long-standing mystery. A new study on Wolbachia's Cif proteins in PLOS Biology provides supportive evidence for the "Host modification model, " although the alternative "Toxin-antidote model" is still in the running

Effect of high molecular weight hyaluronan on cartilage degeneration in a rabbit model of osteoarthritis

SummaryThe effects of high molecular weight hyaluronan (HA) on cartilage degeneration were investigated in a partial menisectomy model of osteoarthritis (OA) in the rabbit knee. This study compared HA80 (0.8 × 106 Da, 1%), HA190 (1.9 × 106 Da, 0.01–1%) and saline. HA (0.1 ml/kg) or saline were injected intra-articularly twice a week immediately after surgery. Degenerative changes in femoral and tibial cartilages were graded histopathologically 2 and 4 weeks after surgery. Two weeks after surgery, HA190, only when used at a 1% concentration, resulted in a dramatic inhibition of cartilage degeneration in both the femoral condyle and the tibial plateau (P < 0.01). Two weeks after surgery, the protection against cartilage degeneration was significantly (P < 0.05) greater with HA190 than with HA80. Four weeks after surgery, only the femoral cartilage degeneration was significantly and similarly inhibited with HA190 (P < 0.01) and HA80 (P < 0.05). Scanning electron micrographs of femoral cartilage showed that cartilage degeneration was less severe with HA190 than with saline. These results might suggest that, in the rabbit model, intra-articular administration of higher molecular weight HA is more effective than lower molecular weight HA in inhibiting cartilage degeneration in early OA

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

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

Self-stabilization mechanism encoded by a bacterial toxin facilitates reproductive parasitism

オス殺しのコストパフォーマンスが高いわけ --共生細菌の毒素は自己安定化のしくみをもつ--. 京都大学プレスリリース. 2023-09-08.A wide variety of maternally transmitted endosymbionts in insects are associated with reproductive parasitism, whereby they interfere with host reproduction to increase the ratio of infected females and spread within populations. Recent successes in identifying bacterial factors responsible for reproductive parasitism as well as further omics approaches have highlighted the common appearance of deubiquitinase domains, although their biological roles—in particular, how they link to distinct manipulative phenotypes—remain poorly defined. Spiroplasma poulsonii is a helical and motile bacterial endosymbiont of Drosophila, which selectively kills male progeny with a male-killing toxin Spaid (S. poulsonii androcidin), which encodes an ovarian tumor (OTU) deubiquitinase domain. Artificial expression of Spaid in flies reproduces male-killing-associated pathologies that include abnormal apoptosis and neural defects during embryogenesis; moreover, it highly accumulates on the dosage-compensated male X chromosome, congruent with cellular defects such as the DNA damage/chromatin bridge breakage specifically induced upon that chromosome. Here, I show that without the function of OTU, Spaid is polyubiquitinated and degraded through the host ubiquitin-proteasome pathway, leading to the attenuation of male-killing activity as shown previously. Furthermore, I find that Spaid utilizes its OTU domain to deubiquitinate itself in an intermolecular manner. Collectively, the deubiquitinase domain of Spaid serves as a self-stabilization mechanism to facilitate male killing in flies, optimizing a molecular strategy of endosymbionts that enables the efficient manipulation of the host at a low energetic cost

平面内細胞極性における微小管動態の制御

京都大学0048新制・課程博士博士(生命科学)甲第16226号生博第213号新制||生||28(附属図書館)28805京都大学大学院生命科学研究科統合生命科学専攻(主査)教授 上村 匡, 教授 荒木 崇, 教授 松崎 文雄学位規則第4条第1項該当Ph.D. (Life Sciences)Kyoto UniversityDA

Male-killing toxin in a bacterial symbiont of Drosophila

Several lineages of symbiotic bacteria in insects selfishly manipulate host reproduction to spread in a population 1 , often by distorting host sex ratios. Spiroplasma poulsonii2,3 is a helical and motile, Gram-positive symbiotic bacterium that resides in a wide range of Drosophila species 4 . A notable feature of S. poulsonii is male killing, whereby the sons of infected female hosts are selectively killed during development1,2. Although male killing caused by S. poulsonii has been studied since the 1950s, its underlying mechanism is unknown. Here we identify an S. poulsonii protein, designated Spaid, whose expression induces male killing. Overexpression of Spaid in D. melanogaster kills males but not females, and induces massive apoptosis and neural defects, recapitulating the pathology observed in S. poulsonii-infected male embryos5-11. Our data suggest that Spaid targets the dosage compensation machinery on the male X chromosome to mediate its effects. Spaid contains ankyrin repeats and a deubiquitinase domain, which are required for its subcellular localization and activity. Moreover, we found a laboratory mutant strain of S. poulsonii with reduced male-killing ability and a large deletion in the spaid locus. Our study has uncovered a bacterial protein that affects host cellular machinery in a sex-specific way, which is likely to be the long-searched-for factor responsible for S. poulsonii-induced male killin

Common and unique strategies of male killing evolved in two distinct Drosophila symbionts

Male killing is a selfish reproductive manipulation caused by symbiotic bacteria, where male offspring of infected hosts are selectively killed. The underlying mechanisms and the process of their evolution are of great interest not only in terms of fundamental biology, but also their potential applications. The two bacterial Drosophila symbionts, Wolbachia and Spiroplasma, have independently evolved male-killing ability. This raises the question whether the underlying mechanisms share some similarities or are specific to each bacterial species. Here, we analyse pathogenic phenotypes of D. bifasciata infected with its natural male-killing Wolbachia strain and compare them with those of D. melanogaster infected with male-killing Spiroplasma. We show that male progeny infected with the Wolbachia strain die during embryogenesis with abnormal apoptosis. Interestingly, male-killing Wolbachia infection induces DNA damage and segregation defects in the dosage-compensated chromosome in male embryos, which are reminiscent of the phenotypes caused by male-killing Spiroplasma in D. melanogaster. By contrast, host neural development seems to proceed normally unlike male-killing Spiroplasma infection. Our results demonstrate that the dosage-compensated chromosome is a common target of two distinct male killers, yet Spiroplasma uniquely evolved the ability to damage neural tissue of male embryos

Male-Killing <i>Spiroplasma</i> Induces Sex-Specific Cell Death via Host Apoptotic Pathway

<div><p>Some symbiotic bacteria cause remarkable reproductive phenotypes like cytoplasmic incompatibility and male-killing in their host insects. Molecular and cellular mechanisms underlying these symbiont-induced reproductive pathologies are of great interest but poorly understood. In this study, <i>Drosophila melanogaster</i> and its native <i>Spiroplasma</i> symbiont strain MSRO were investigated as to how the host's molecular, cellular and morphogenetic pathways are involved in the symbiont-induced male-killing during embryogenesis. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, anti-cleaved-Caspase-3 antibody staining, and apoptosis-deficient mutant analysis unequivocally demonstrated that the host's apoptotic pathway is involved in <i>Spiroplasma</i>-induced male-specific embryonic cell death. Double-staining with TUNEL and an antibody recognizing epidermal marker showed that embryonic epithelium is the main target of <i>Spiroplasma</i>-induced male-specific apoptosis. Immunostaining with antibodies against markers of differentiated and precursor neural cells visualized severe neural defects specifically in <i>Spiroplasma</i>-infected male embryos as reported in previous studies. However, few TUNEL signals were detected in the degenerate nervous tissues of male embryos, and the <i>Spiroplasma</i>-induced neural defects in male embryos were not suppressed in an apoptosis-deficient host mutant. These results suggest the possibility that the apoptosis-dependent epidermal cell death and the apoptosis-independent neural malformation may represent different mechanisms underlying the <i>Spiroplasma</i>-induced male-killing. Despite the male-specific progressive embryonic abnormality, <i>Spiroplasma</i> titers remained almost constant throughout the observed stages of embryonic development and across male and female embryos. Strikingly, a few <i>Spiroplasma</i>-infected embryos exhibited gynandromorphism, wherein apoptotic cell death was restricted to male cells. These observations suggest that neither quantity nor proliferation of <i>Spiroplasma</i> cells but some <i>Spiroplasma</i>-derived factor(s) may be responsible for the expression of the male-killing phenotype.</p></div

Supplementary material from Common and unique strategies of male killing evolved in two distinct <i>Drosophila</i> symbionts

Supplementary methods, references, table, and figures