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Self-stabilization mechanism encoded by a bacterial toxin facilitates reproductive parasitism
Open accessPublished version of a preprint
Abstract
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.1,2 Recent successes in identifying bacterial factors responsible for reproductive parasitism 3,4,5,6,7 as well as further omics approaches 8,9,10,11,12 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,13,14 which selectively kills male progeny with a male-killing toxin Spaid (S. poulsonii androcidin), which encodes an ovarian tumor (OTU) deubiquitinase domain.6 Artificial expression of Spaid in flies reproduces male-killing-associated pathologies that include abnormal apoptosis and neural defects during embryogenesis 6,15,16,17,18,19; moreover, it highly accumulates on the dosage-compensated male X chromosome,20 congruent with cellular defects such as the DNA damage/chromatin bridge breakage specifically induced upon that chromosome.6,21,22,23 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.6 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.
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Citations
Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
The Phyre2 web portal for protein modeling, prediction and analysis
Kelley, L. A., Mezulis, S., Yates, C. M., Wass, M. N., & Sternberg, M. J. E. (2015) · Nature Protocols · doi:10.1038/nprot.2015.053 · Cited by 9,652
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes
Brand, A. H., & Perrimon, N. (1993) · Development · doi:10.1242/dev.118.2.401 · Cited by 9,612
ColabFold - Making protein folding accessible to all
Mirdita, M., Schütze, K., Moriwaki, Y., Heo, L., Ovchinnikov, S., & Steinegger, M. (2021) · doi:10.1101/2021.08.15.456425 · Cited by 9,391
Hershko, A., & Ciechanover, A. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.425 · Cited by 8,840
Komander, D., & Rape, M. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060310-170328 · Cited by 3,679
Wolbachia: master manipulators of invertebrate biology
Werren, J. H., Baldo, L., & Clark, M. E. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1969 · Cited by 2,819
The InterPro protein families and domains database: 20 years on
Blum, M., Chang, H.-Y., Chuguransky, S., Grego, T., Kandasaamy, S., Mitchell, A., Nuka, G., Paysan-Lafosse, T., Qureshi, M., Raj, S., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa977 · Cited by 2,231
Rawlings, N. D., Barrett, A. J., Thomas, P. D., Huang, X., Bateman, A., & Finn, R. D. (2018) · Nucleic Acids Research · doi:10.1093/nar/gkx1134 · Cited by 1,749
Ubiquitin ligases: structure, function, and regulation
Zheng, N., & Shabek, N. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014922 · Cited by 1,499
Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes.
Reyes-Turcu, F. E., Ventii, K. H., & Wilkinson, K. D. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.082307.091526 · Cited by 1,396
Phylogeny and PCR–based classification of Wolbachia strains using wsp gene sequences
Zhou, W., Rousset, F., & O'Neill, S. (1998) · Proceedings of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rspb.1998.0324 · Cited by 1,318
Dali server: structural unification of protein families
Holm, L. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac387 · Cited by 935
EBImage—an R package for image processing with applications to cellular phenotypes
Pau, G., Fuchs, F., Sklyar, O., Boutros, M., & Huber, W. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq046 · Cited by 797
Gal4 in the Drosophila female germline
Rørth, P. (1998) · Mechanisms of Development · doi:10.1016/s0925-4773(98)00157-9 · Cited by 638
A single female-specific piRNA is the primary determiner of sex in the silkworm
Kiuchi, T., Koga, H., Kawamoto, M., Shoji, K., Sakai, H., Arai, Y., Ishihara, G., Kawaoka, S., Sugano, S., Shimada, T., et al. (2014) · Nature · doi:10.1038/nature13315 · Cited by 521
Non-parametric Statistical Methods
Gastwirth, J. L. (1990) · Time Series and Statistics · doi:10.1007/978-1-349-20865-4_24 · Cited by 514
Prophage WO genes recapitulate and enhance Wolbachia-induced cytoplasmic incompatibility
LePage, D. P., Metcalf, J. A., Bordenstein, S. R., On, J., Perlmutter, J. I., Shropshire, J. D., Layton, E. M., Funkhouser-Jones, L. J., Beckmann, J. F., & Bordenstein, S. R. (2017) · Nature · doi:10.1038/nature21391 · Cited by 464
Edelheit, O., Hanukoglu, A., & Hanukoglu, I. (2009) · BMC Biotechnology · doi:10.1186/1472-6750-9-61 · Cited by 397
A Wolbachia deubiquitylating enzyme induces cytoplasmic incompatibility
Beckmann, J. F., Ronau, J. A., & Hochstrasser, M. (2017) · Nature Microbiology · doi:10.1038/nmicrobiol.2017.7 · Cited by 374
Intracellular localization of proteasomes
Wójcik, C., & DeMartino, G. N. (2003) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00380-1 · Cited by 352
Makarova, K. S., Aravind, L., & Koonin, E. V. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01530-3 · Cited by 282
Functional diversity of ankyrin repeats in microbial proteins
Khodor, S. A., Price, C. T. D., Kalia, A., & Kwaik, Y. A. (2009) · Trends in Microbiology · doi:10.1016/j.tim.2009.11.004 · Cited by 227
Viral avoidance and exploitation of the ubiquitin system
Randow, F., & Lehner, P. J. (2009) · Nature Cell Biology · doi:10.1038/ncb0509-527 · Cited by 212
Dosage Compensation inDrosophilaPreprint
Lucchesi, J. C., & Kuroda, M. I. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a019398 · Cited by 212
Mashtalir, N., Daou, S., Barbour, H., Nkwe, N. S., Gagnon, J. K., Hammond-Martel, I., Dar, H. H., Therrien, M., & Affar, E. B. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.002 · Cited by 200
Deubiquitinase USP37 Is Activated by CDK2 to Antagonize APCCDH1 and Promote S Phase Entry
Huang, X., Summers, M. K., Pham, V. C., Lill, J. R., Liu, J., Lee, G., Kirkpatrick, D. S., Jackson, P. K., Fang, G., & Dixit, V. M. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.03.027 · Cited by 162
Burdette, W. J. (1963) · Cited by 160
Eukaryotic association module in phage WO genomes from Wolbachia
Bordenstein, S. R., & Bordenstein, S. R. (2016) · Nature Communications · doi:10.1038/ncomms13155 · Cited by 159
Male-killing toxin in a bacterial symbiont of Drosophila
Harumoto, T., & Lemaître, B. (2018) · Nature · doi:10.1038/s41586-018-0086-2 · Cited by 158
Self-citationReproductive Parasitism: Maternally Inherited Symbionts in a Biparental WorldPreprint
Hurst, G. D. D., & Frost, C. L. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a017699 · Cited by 155
Male‐killing Spiroplasma naturally infecting Drosophila melanogaster
Montenegro, H., Solferini, V. N., Klaczko, L. B., & Hurst, G. D. D. (2005) · Insect Molecular Biology · doi:10.1111/j.1365-2583.2005.00558.x · Cited by 125
Fukui, T., Kawamoto, M., Shoji, K., Kiuchi, T., Sugano, S., Shimada, T., Suzuki, Y., & Katsuma, S. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1005048 · Cited by 115
Beckmann, J. F., & Fallon, A. M. (2013) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2013.07.002 · Cited by 114
The phage gene wmk is a candidate for male killing by a bacterial endosymbiont
Perlmutter, J. I., Bordenstein, S. R., Unckless, R. L., LePage, D. P., Metcalf, J. A., Hill, T., Martinez, J., Jiggins, F. M., & Bordenstein, S. R. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007936 · Cited by 102
A Functional Dosage Compensation Complex Required for Male Killing in Drosophila
Veneti, Z., Bentley, J. K., Koana, T., Braig, H. R., & Hurst, G. D. D. (2005) · Science · doi:10.1126/science.1107182 · Cited by 99
Lee, S. Y., Ramírez, J., Franco, M., Lectez, B. L. P., González-Lopez, M., Barrio, R., & Mayor, U. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1526-7 · Cited by 94
Ankyrin domains across the Tree of Life
Jernigan, K. K., & Bordenstein, S. R. (2014) · PeerJ · doi:10.7717/peerj.264 · Cited by 93
A Wolbachia factor for male killing in lepidopteran insects
Katsuma, S., Hirota, K., Matsuda–Imai, N., Fukui, T., Muro, T., Nishino, K., Kosako, H., Shoji, K., Takanashi, H., Fujii, T., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34488-y · Cited by 82
USP4 Auto-Deubiquitylation Promotes Homologous Recombination
Wijnhoven, P. W. G., Konietzny, R., Blackford, A. N., Travers, J., Kessler, B. M., Nishi, R., & Jackson, S. P. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.09.019 · Cited by 78
Exploitation of the host cell ubiquitin machinery by microbial effector proteins
Lin, Y.-H., & Machner, M. P. (2017) · Journal of Cell Science · doi:10.1242/jcs.188482 · Cited by 73
The Spiroplasma heritable bacterial endosymbiont of Drosophila
Haselkorn, T. S. (2010) · Fly · doi:10.4161/fly.4.1.10883 · Cited by 72
Families and clans of cysteine peptidases
Barrett, A. J., & Rawlings, N. D. (1996) · Perspectives in Drug Discovery and Design · doi:10.1007/bf02174042 · Cited by 67
Kubori, T., Kitao, T., Ando, H., & Nagai, H. (2018) · Cellular Microbiology · doi:10.1111/cmi.12840 · Cited by 67
Denuc, A., Bosch-Comas, A., Gonzàlez‐Duarte, R., & Marfany, G. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005571 · Cited by 66
Pool, J. E., Wong, A., & Aquadro, C. F. (2006) · Heredity · doi:10.1038/sj.hdy.6800830 · Cited by 62
Paternal transmission of the Wolbachia CidB toxin underlies cytoplasmic incompatibility
Horard, B., Terretaz, K., Grenet, A.-S. G., et al. (2022) · Current Biology · doi:10.1016/j.cub.2022.01.052 · Cited by 62
Identification and characterization of diverse OTU deubiquitinases in bacteria
Schubert, A. F., Nguyen, J. V., Franklin, T. G., Geurink, P. P., Roberts, C. G., Sanderson, D. J., Miller, L. N., Ovaa, H., Hofmann, K., Pruneda, J. N., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2020105127 · Cited by 61
Male-killing symbiont damages host’s dosage-compensated sex chromosome to induce embryonic apoptosis
Harumoto, T., Anbutsu, H., Lemaître, B., & Fukatsu, T. (2016) · Nature Communications · doi:10.1038/ncomms12781 · Cited by 55
Self-citationA Tangled Web: Origins of Reproductive Parasitism
Gillespie, J. J., Driscoll, T., Verhoeve, V. I., Rahman, M. S., Macaluso, K. R., & Azad, A. F. (2018) · Genome Biology and Evolution · doi:10.1093/gbe/evy159 · Cited by 55
The ubiquitin ligation machinery in the defense against bacterial pathogens
Tripathi‐Giesgen, I., Behrends, C., & Alpi, A. F. (2021) · EMBO Reports · doi:10.15252/embr.202152864 · Cited by 55
UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself
Wada, K., & Kamitani, T. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.01.144 · Cited by 53
Infective Transfer of Maternally Inherited Abnormal Sex-Ratio in Drosophila willistoni
Malogolowkin, C., & Poulson, D. F. (1957) · Science · doi:10.1126/science.126.3262.32 · Cited by 52
Calcium/Calmodulin Regulates Ubiquitination of the Ubiquitin-specific Protease TRE17/USP6
Shen, C., Ye, Y., Robertson, S. E., Lau, A. W., Mak, D. D., & Chou, M. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505220200 · Cited by 52
Bacterial DUBs: deubiquitination beyond the seven classes
Hermanns, T., & Hofmann, K. (2019) · Biochemical Society Transactions · doi:10.1042/bst20190526 · Cited by 51
Liu, S., Luo, J., Zhen, X., Qiu, J., Ouyang, S., & Luo, Z. (2020) · eLife · doi:10.7554/elife.58114 · Cited by 51
Diversity and function of arthropod endosymbiont toxins
Massey, J. H., & Newton, I. L. G. (2021) · Trends in Microbiology · doi:10.1016/j.tim.2021.06.008 · Cited by 47
Developmental effects of the sex‐ratio agent in embryos of Drosophila willistoni
Counce, S. J., & Poulson, D. F. (1962) · Journal of Experimental Zoology · doi:10.1002/jez.1401510103 · Cited by 46
Rapid molecular evolution of Spiroplasma symbionts of Drosophila
Gerth, M., Martínez-Montoya, H., Ramirez, P., Masson, F., Griffin, J. S., Aramayo, R., Siozios, S., Lemaître, B., Mateos, M., & Hurst, G. D. D. (2021) · Microbial Genomics · doi:10.1099/mgen.0.000503 · Cited by 46
Bacterial OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection
Shin, D., Bhattacharya, A., Cheng, Y.-L., Alonso, M. C., Mehdipour, A. R., van Noort, G. J. V. D. H., Ovaa, H., Hummer, G., & Đikić, I. (2020) · eLife · doi:10.7554/elife.58277 · Cited by 45
Furtado, A. R., Essid, M., Perrinet, S., Balañá, M. E., Yoder, N. C., Dehoux, P., & Subtil, A. (2013) · Cellular Microbiology · doi:10.1111/cmi.12171 · Cited by 44
Viral OTU Deubiquitinases: A Structural and Functional Comparison
Bailey-Elkin, B. A., van Kasteren, P. B., Snijder, E. J., Kikkert, M., & Mark, B. L. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1003894 · Cited by 43
Sex determination systems as the interface between male-killing bacteria and their hosts
Hornett, E. A., Kageyama, D., & Hurst, G. D. D. (2022) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2021.2781 · Cited by 43
Bentley, J. K., Veneti, Z., Heraty, J., & Hurst, G. D. D. (2007) · BMC Biology · doi:10.1186/1741-7007-5-9 · Cited by 40
Male-Killing Spiroplasma Induces Sex-Specific Cell Death via Host Apoptotic Pathway
Harumoto, T., Anbutsu, H., & Fukatsu, T. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1003956 · Cited by 37
Self-citationMa, K., Zhen, X., Zhou, B., Gan, N., Cao, Y., Fan, C., Ouyang, S., Luo, Z., & Qiu, J. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011758 · Cited by 37
Beckmann, J. F., Vaerenberghe, K. V., Akwa, D. E., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2113271118 · Cited by 30
Cheng, B., Kuppanda, N., Aldrich, J. C., Akbari, O. S., & Ferree, P. M. (2016) · Current Biology · doi:10.1016/j.cub.2016.03.050 · Cited by 29
Martin, J., Chong, T. N., & Ferree, P. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079368 · Cited by 25
Terretaz, K., Horard, B., Weill, M., Loppin, B., & Landmann, F. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011211 · Cited by 20
Self-stabilizing regulation of deubiquitinating enzymes in an enzymatic activity-dependent manner
Hou, Z., Shi, W., Feng, J., Wang, W., Zheng, E., Lin, H., Cheng, Y., & Li, L. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.04.073 · Cited by 9
Research works printed but not linked: 1
- Tsuchiyama-Omura, 1988, Morphological features of embryogenesis in Drosophila melanogaster infected with a male-killing Spiroplasma, Zool. Sci., 5, 375
Metadata
- Authors
- Harumoto, T.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Harumoto, Toshiyuki
- ORCID
- Harumoto, Toshiyuki
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2023-09
- Volume
- 33
- Issue
- 18
- Pages
- 4021-4029.e6
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W4386444034
- Cited by
- 12
- References
- 72
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 1
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 390 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by-nc-nd)
- Funders
- Japan Society for the Promotion of Science (22K19352)
- Exploratory Research for Advanced Technology (JPMJER1902)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Insect Science › Insect symbiosis and bacterial influences
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Animal Behavior and Reproduction
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytoplasmas and Hemiptera pathogens
- Keywords
- reproductive parasitism, Wolbachia, bacterial toxins, self-stabilization, cytoplasmic incompatibility, insect reproduction, host-parasite interactions
- MeSH terms
- Animals, Bacterial Toxins, Drosophila melanogaster, Female, Male, Reproduction, Spiroplasma, Symbiosis
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