Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection.

التفاصيل البيبلوغرافية
العنوان:	Bacterial reprogramming of tick metabolism impacts vector fitness and susceptibility to infection.
المؤلفون:	Samaddar S; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA., Rolandelli A; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA., O'Neal AJ; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA.; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Laukaitis-Yousey HJ; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA., Marnin L; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA., Singh N; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA.; Department of Biotechnology, School of Energy Technology, Pandit Deendayal Energy University; Knowledge Corridor, Gandhinagar, India., Wang X; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA.; MP Biomedicals, Solon, OH, USA., Butler LR; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA.; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Rangghran P; Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, School of Medicine, University of Maryland, Baltimore, MD, USA., Kitsou C; Department of Veterinary Medicine, University of Maryland, College Park, MD, USA., Cabrera Paz FE; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA., Valencia L; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA., R Ferraz C; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA., Munderloh UG; Department of Entomology, University of Minnesota, Saint Paul, MN, USA., Khoo B; Division of Environmental Health Sciences, University of Minnesota, Minneapolis, MN, USA., Cull B; Department of Entomology, University of Minnesota, Saint Paul, MN, USA., Rosche KL; Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA., Shaw DK; Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA, USA., Oliver J; Division of Environmental Health Sciences, University of Minnesota, Minneapolis, MN, USA., Narasimhan S; Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA., Fikrig E; Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA., Pal U; Department of Veterinary Medicine, University of Maryland, College Park, MD, USA., Fiskum GM; Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, School of Medicine, University of Maryland, Baltimore, MD, USA., Polster BM; Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, School of Medicine, University of Maryland, Baltimore, MD, USA., Pedra JHF; Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD, USA. jpedra@som.umaryland.edu.
المصدر:	Nature microbiology [Nat Microbiol] 2024 Sep; Vol. 9 (9), pp. 2278-2291. Date of Electronic Publication: 2024 Jul 12.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101674869 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2058-5276 (Electronic) Linking ISSN: 20585276 NLM ISO Abbreviation: Nat Microbiol Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: [London] : Nature Publishing Group, [2016]-
مواضيع طبية MeSH:	Ixodes/microbiology , Anaplasma phagocytophilum/metabolism , Anaplasma phagocytophilum/genetics , Rickettsia/genetics , Rickettsia/metabolism , Borrelia burgdorferi/genetics , Borrelia burgdorferi*/metabolism, Animals ; Mice ; Lyme Disease/microbiology ; Glycolysis ; Metabolomics ; Humans ; Genetic Fitness ; Symbiosis
مستخلص:	Arthropod-borne pathogens are responsible for hundreds of millions of infections in humans each year. The blacklegged tick, Ixodes scapularis, is the predominant arthropod vector in the United States and is responsible for transmitting several human pathogens, including the Lyme disease spirochete Borrelia burgdorferi and the obligate intracellular rickettsial bacterium Anaplasma phagocytophilum, which causes human granulocytic anaplasmosis. However, tick metabolic response to microbes and whether metabolite allocation occurs upon infection remain unknown. Here we investigated metabolic reprogramming in the tick ectoparasite I. scapularis and determined that the rickettsial bacterium A. phagocytophilum and the spirochete B. burgdorferi induced glycolysis in tick cells. Surprisingly, the endosymbiont Rickettsia buchneri had a minimal effect on bioenergetics. An unbiased metabolomics approach following A. phagocytophilum infection of tick cells showed alterations in carbohydrate, lipid, nucleotide and protein metabolism, including elevated levels of the pleiotropic metabolite β-aminoisobutyric acid. We manipulated the expression of genes associated with β-aminoisobutyric acid metabolism in I. scapularis, resulting in feeding impairment, diminished survival and reduced bacterial acquisition post haematophagy. Collectively, we discovered that metabolic reprogramming affects interspecies relationships and fitness in the clinically relevant tick I. scapularis. (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
التعليقات:	Update of: bioRxiv. 2023 May 26:2023.05.26.542501. doi: 10.1101/2023.05.26.542501. (PMID: 37292783)
References:	Vector-borne Diseases (WHO, 2020); https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases. Kurokawa, C. et al. Interactions between Borrelia burgdorferi and ticks. Nat. Rev. Microbiol. 18, 587–600 (2020). (PMID: 32651470735153610.1038/s41579-020-0400-5) Lochhead, R. B., Strle, K., Arvikar, S. L., Weis, J. J. & Steere, A. C. Lyme arthritis: linking infection, inflammation and autoimmunity. Nat. Rev. Rheumatol. 17, 449–461 (2021). (PMID: 34226730948858710.1038/s41584-021-00648-5) O’Neal, A. J., Singh, N., Mendes, M. T. & Pedra, J. H. F. The genus Anaplasma: drawing back the curtain on tick–pathogen interactions. Pathog. Dis. 79, ftab022 (2021). (PMID: 33792663806223510.1093/femspd/ftab022) Smith, R. P. Tick-borne diseases of humans. Emerg. Infect. Dis. 11, 1808–1809 (2005). (PMID: 336734210.3201/eid1111.051160) Verhoeve, V. I., Fauntleroy, T. D., Risteen, R. G., Driscoll, T. P. & Gillespie, J. J. Cryptic genes for interbacterial antagonism distinguish Rickettsia species infecting blacklegged ticks from other Rickettsia pathogens. Front. Cell Infect. Microbiol. 12, 880813 (2022). (PMID: 35592653911174510.3389/fcimb.2022.880813) Hagen, R., Verhoeve, V. I., Gillespie, J. J. & Driscoll, T. P. Conjugative transposons and their cargo genes vary across natural populations of Rickettsia buchneri infecting the tick Ixodes scapularis. Genome Biol. Evol. 10, 3218–3229 (2018). (PMID: 30398619630007210.1093/gbe/evy247) Kurtti, T. J. et al. Rickettsia buchneri sp. nov., a rickettsial endosymbiont of the blacklegged tick Ixodes scapularis. Int. J. Syst. Evol. Microbiol. 65, 965–970 (2015). (PMID: 25563918436529210.1099/ijs.0.000047) Cabezas-Cruz, A., Espinosa, P., Alberdi, P. & de la Fuente, J. Tick–pathogen interactions: the metabolic perspective. Trends Parasitol. 35, 316–328 (2019). (PMID: 3071143710.1016/j.pt.2019.01.006) Samaddar, S., Marnin, L., Butler, L. R. & Pedra, J. H. F. Immunometabolism in arthropod vectors: redefining interspecies relationships. Trends Parasitol. 36, 807–815 (2020). (PMID: 32819827789751110.1016/j.pt.2020.07.010) Shaw, D. K. et al. Vector immunity and evolutionary ecology: the harmonious dissonance. Trends Immunol. 39, 862–873 (2018). (PMID: 30301592621829710.1016/j.it.2018.09.003) Boggs, C. Resource allocation: exploring connections between foraging and life history. Funct. Ecol. 6, 508–518 (1992). (PMID: 10.2307/2390047) Roff, D. Evolution of Life Histories: Theory and Analysis (Springer Science & Business Media, 1993). Stearns, S. C., Rose, M. R. & Mueller, L. D. The evolution of life histories. J. Evol. Biol. 6, 304–306 (1992). Burger, J. R., Hou, C. & Brown, J. H. Toward a metabolic theory of life history. Proc. Natl Acad. Sci. USA 116, 26653–26661 (2019). (PMID: 31822607693634610.1073/pnas.1907702116) Wang, A., Luan, H. H. & Medzhitov, R. An evolutionary perspective on immunometabolism. Science 363, eaar3932 (2019). Russell, D. G., Huang, L. & VanderVen, B. C. Immunometabolism at the interface between macrophages and pathogens. Nat. Rev. Immunol. 19, 291–304 (2019). (PMID: 30679807703256010.1038/s41577-019-0124-9) Warburg, O., Posener, K. & Negelein, E. Über den stoffwechsel der carcinomzelle. Naturwissenschaften 12, 1131–1137 (1924). (PMID: 10.1007/BF01504608) Ward, P. S. & Thompson, C. B. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell 21, 297–308 (2012). (PMID: 22439925331199810.1016/j.ccr.2012.02.014) DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G. & Thompson, C. B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 7, 11–20 (2008). (PMID: 1817772110.1016/j.cmet.2007.10.002) Hall, S. R., Simonis, J. L., Nisbet, R. M., Tessier, A. J. & Cáceres, C. E. Resource ecology of virulence in a planktonic host–parasite system: an explanation using dynamic energy budgets. Am. Nat. 174, 149–162 (2009). (PMID: 1952711910.1086/600086) Peyraud, R., Cottret, L., Marmiesse, L., Gouzy, J. & Genin, S. A resource allocation trade-off between virulence and proliferation drives metabolic versatility in the plant pathogen Ralstonia solanacearum. PLoS Pathog. 12, e1005939 (2016). (PMID: 27732672506143110.1371/journal.ppat.1005939) Hite, J. L., Pfenning, A. C. & Cressler, C. E. Starving the enemy? Feeding behavior shapes host–parasite interactions. Trends Ecol. Evol. 35, 68–80 (2020). (PMID: 3160459310.1016/j.tree.2019.08.004) Cressler, C. E., Nelson, W. A., Day, T. & McCauley, E. Disentangling the interaction among host resources, the immune system and pathogens. Ecol. Lett. 17, 284–293 (2014). (PMID: 2435097410.1111/ele.12229) Voss, K. et al. A guide to interrogating immunometabolism. Nat. Rev. Immunol. 21, 637–652 (2021). (PMID: 33859379847871010.1038/s41577-021-00529-8) Song, X., Zhong, Z., Gao, L., Weiss, B. L. & Wang, J. Metabolic interactions between disease-transmitting vectors and their microbiota. Trends Parasitol. 38, 697–708 (2022). (PMID: 3564385310.1016/j.pt.2022.05.002) Hoxmeier, J. C. et al. Metabolomics of the tick–Borrelia interaction during the nymphal tick blood meal. Sci. Rep. 7, 1–11 (2017). (PMID: 10.1038/srep44394) Cabezas-Cruz, A., Alberdi, P., Valdes, J. J., Villar, M. & de la Fuente, J. Anaplasma phagocytophilum infection subverts carbohydrate metabolic pathways in the tick vector, Ixodes scapularis. Front. Cell Infect. Microbiol. 7, 23 (2017). (PMID: 28229048529376410.3389/fcimb.2017.00023) Alberdi, P. et al. The redox metabolic pathways function to limit Anaplasma phagocytophilum infection and multiplication while preserving fitness in tick vector cells. Sci. Rep. 9, 13236 (2019). (PMID: 31520000674449910.1038/s41598-019-49766-x) Dahmani, M., Anderson, J. F., Sultana, H. & Neelakanta, G. Rickettsial pathogen uses arthropod tryptophan pathway metabolites to evade reactive oxygen species in tick cells. Cell. Microbiol. 22, e13237 (2020). (PMID: 32562372748332410.1111/cmi.13237) Namjoshi, P., Dahmani, M., Sultana, H. & Neelakanta, G. Rickettsial pathogen inhibits tick cell death through tryptophan metabolite mediated activation of p38 MAP kinase. iScience 26, 105730 (2023). (PMID: 3658283310.1016/j.isci.2022.105730) Villar, M. et al. Integrated metabolomics, transcriptomics and proteomics identifies metabolic pathways affected by Anaplasma phagocytophilum infection in tick cells. Mol. Cell. Proteomics 14, 3154–3172 (2015). (PMID: 26424601476261510.1074/mcp.M115.051938) Mookerjee, S. A., Gerencser, A. A., Nicholls, D. G. & Brand, M. D. Quantifying intracellular rates of glycolytic and oxidative ATP production and consumption using extracellular flux measurements. J. Biol. Chem. 292, 7189–7207 (2017). (PMID: 28270511540948610.1074/jbc.M116.774471) Nicholls, D. G. et al. Bioenergetic profile experiment using C2C12 myoblast cells. J. Vis. Exp. 46, e2511 (2010). Munderloh, U. G., Liu, Y., Wang, M., Chen, C. & Kurtti, T. J. Establishment, maintenance and description of cell lines from the tick Ixodes scapularis. J. Parasitol. 80, 533–543 (1994). (PMID: 806452010.2307/3283188) Troughton, D. R. & Levin, M. L. Life cycles of seven ixodid tick species (Acari: Ixodidae) under standardized laboratory conditions. J. Med. Entomol. 44, 732–740 (2007). (PMID: 1791550210.1093/jmedent/44.5.732) Kocan, K. M., de la Fuente, J. & Coburn, L. A. Insights into the development of Ixodes scapularis: a resource for research on a medically important tick species. Parasit. Vectors 8, 592 (2015). (PMID: 26576940465033810.1186/s13071-015-1185-7) Troha, K. & Ayres, J. S. Metabolic adaptations to infections at the organismal level. Trends Immunol. 41, 113–125 (2020). (PMID: 31959515740965610.1016/j.it.2019.12.001) Rosenberg, G., Riquelme, S., Prince, A. & Avraham, R. Immunometabolic crosstalk during bacterial infection. Nat. Microbiol. 7, 497–507 (2022). (PMID: 3536578410.1038/s41564-022-01080-5) Thapa, S., Zhang, Y. & Allen, M. S. Bacterial microbiomes of Ixodes scapularis ticks collected from Massachusetts and Texas, USA. BMC Microbiol. 19, 138 (2019). (PMID: 31234774659183910.1186/s12866-019-1514-7) Van Treuren, W. et al. Variation in the microbiota of Ixodes ticks with regard to geography, species, and sex. Appl. Environ. Microbiol. 81, 6200–6209 (2015). (PMID: 26150449454225210.1128/AEM.01562-15) Roberts, L. D. et al. β-aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metab. 19, 96–108 (2014). (PMID: 24411942401735510.1016/j.cmet.2013.12.003) Tanianskii, D. A., Jarzebska, N., Birkenfeld, A. L., O’Sullivan, J. F. & Rodionov, R. N. β-aminoisobutyric acid as a novel regulator of carbohydrate and lipid metabolism. Nutrients 11, 524 (2019). (PMID: 30823446647058010.3390/nu11030524) Sharma, A. et al. Cas9-mediated gene editing in the black-legged tick, Ixodes scapularis, by embryo injection and ReMOT Control. iScience 25, 103781 (2022). (PMID: 35535206907689010.1016/j.isci.2022.103781) Sawada, M., Yamamoto, H., Ogasahara, A., Tanaka, Y. & Kihara, S. β-aminoisobutyric acid protects against vascular inflammation through PGC-1β-induced antioxidative properties. Biochem. Biophys. Res. Commun. 516, 963–968 (2019). (PMID: 3127794710.1016/j.bbrc.2019.06.141) Kitase, Y. et al. β-aminoisobutyric acid, BAIBA, is a muscle-derived osteocyte survival factor. Cell Rep. 22, 1531–1544 (2018). (PMID: 29425508583235910.1016/j.celrep.2018.01.041) Zhu, X. W., Ding, K., Dai, X. Y. & Ling, W. Q. β-aminoisobutyric acid accelerates the proliferation and differentiation of MC3T3-E1 cells via moderate activation of ROS signaling. J. Chin. Med. Assoc. 81, 611–618 (2018). (PMID: 2965041710.1016/j.jcma.2017.12.005) Alasmari, S. & Wall, R. Determining the total energy budget of the tick Ixodes ricinus. Exp. Appl. Acarol. 80, 531–541 (2020). (PMID: 3217053610.1007/s10493-020-00479-1) Corona, A. & Schwartz, I. Borrelia burgdorferi: carbon metabolism and the tick-mammal enzootic cycle. Microbiol. Spectr. 3, 10 (2015). (PMID: 10.1128/microbiolspec.MBP-0011-2014) Rikihisa, Y. Mechanisms of obligatory intracellular infection with Anaplasma phagocytophilum. Clin. Microbiol. Rev. 24, 469–489 (2011). (PMID: 21734244313106310.1128/CMR.00064-10) Driscoll, T. P. et al. Wholly Rickettsia! reconstructed metabolic profile of the quintessential bacterial parasite of eukaryotic cells. MBio 8, e00859–17 (2017). (PMID: 28951473561519410.1128/mBio.00859-17) Dumler, J. S. et al. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and ‘HGE agent’ as subjective synonyms of Ehrlichia phagocytophila. Int. J. Syst. Evol. Microbiol. 51, 2145–2165 (2001). (PMID: 1176095810.1099/00207713-51-6-2145) Narasimhan, S. et al. Grappling with the tick microbiome. Trends Parasitol. 37, 722–733 (2021). (PMID: 33962878828263810.1016/j.pt.2021.04.004) Gillespie, J. J. et al. A Rickettsia genome overrun by mobile genetic elements provides insight into the acquisition of genes characteristic of an obligate intracellular lifestyle. J. Bacteriol. 194, 376–394 (2012). (PMID: 22056929325663410.1128/JB.06244-11) Xiong, Q., Lin, M., Huang, W. & Rikihisa, Y. Infection by Anaplasma phagocytophilum requires recruitment of low-density lipoprotein cholesterol by flotillins. MBio 10, e02783–18 (2019). (PMID: 30914515643705910.1128/mBio.02783-18) Villar, M. et al. Identification and characterization of Anaplasma phagocytophilum proteins involved in infection of the tick vector, Ixodes scapularis. PLoS ONE 10, e0137237 (2015). (PMID: 26340562456037710.1371/journal.pone.0137237) Villar, M. et al. The intracellular bacterium Anaplasma phagocytophilum selectively manipulates the levels of vertebrate host proteins in the tick vector Ixodes scapularis. Parasit. Vectors 9, 467 (2016). (PMID: 27561965500043610.1186/s13071-016-1747-3) Truchan, H. K. et al. Anaplasma phagocytophilum Rab10-dependent parasitism of the trans-Golgi network is critical for completion of the infection cycle. Cell. Microbiol. 18, 260–281 (2016). (PMID: 2628911510.1111/cmi.12500) Shi, C. X. et al. β-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes. Sci. Rep. 6, 21924 (2016). (PMID: 26907958476482910.1038/srep21924) Audzeyenka, I. et al. β-aminoisobutyric acid (L-BAIBA) is a novel regulator of mitochondrial biogenesis and respiratory function in human podocytes. Sci. Rep. 13, 766 (2023). (PMID: 36641502984061310.1038/s41598-023-27914-8) Oliva Chávez, A. S. et al. Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection. Nat. Commun. 12, 3696 (2021). (PMID: 34140472821169110.1038/s41467-021-23900-8) Yoshiie, K., Kim, H. Y., Mott, J. & Rikihisa, Y. Intracellular infection by the human granulocytic ehrlichiosis agent inhibits human neutrophil apoptosis. Infect. Immun. 68, 1125–1133 (2000). (PMID: 106789169725710.1128/IAI.68.3.1125-1133.2000) Labandeira-Rey, M. & Skare, J. T. Decreased infectivity in Borrelia burgdorferi strain B31 is associated with loss of linear plasmid 25 or 28-1. Infect. Immun. 69, 446–455 (2001). (PMID: 111195369790210.1128/IAI.69.1.446-455.2001) Shaw, D. K. et al. Infection-derived lipids elicit an immune deficiency circuit in arthropods. Nat. Commun. 8, 14401 (2017). (PMID: 28195158531688610.1038/ncomms14401) Collet, T.-H. et al. A metabolomic signature of acute caloric restriction. J. Clin. Endocrinol. Metab. 102, 4486–4495 (2017). (PMID: 29029202571870110.1210/jc.2017-01020) Evans, A. et al. High resolution mass spectrometry improves data quantity and quality as compared to unit mass resolution mass spectrometry in high-throughput profiling metabolomics. Metabolomics 4, 1 (2014). DeHaven, C. D., Evans, A. M., Dai, H. & Lawton, K. A. Organization of GC/MS and LC/MS metabolomics data into chemical libraries. J. Cheminform. 2, 9 (2010). (PMID: 20955607298439710.1186/1758-2946-2-9) Sidak-Loftis, L. C. et al. The unfolded-protein response triggers the arthropod immune deficiency pathway. MBio 13, e00703–e00722 (2022). (PMID: 358627819426425)
معلومات مُعتمدة:	F31 AI152215 United States AI NIAID NIH HHS; F31AI152215 U.S. Department of Health & Human Services \| NIH \| National Institute of Allergy and Infectious Diseases (NIAID); T32AI162579 U.S. Department of Health & Human Services \| NIH \| National Institute of Allergy and Infectious Diseases (NIAID); P01 AI138949 United States AI NIAID NIH HHS; R01AI162819 U.S. Department of Health & Human Services \| NIH \| National Institute of Allergy and Infectious Diseases (NIAID); P01AI138949, R01AI080615 U.S. Department of Health & Human Services \| NIH \| National Institute of Allergy and Infectious Diseases (NIAID); R21 AI165520 United States AI NIAID NIH HHS; R01 AI116523 United States AI NIAID NIH HHS; F31AI167471 U.S. Department of Health & Human Services \| NIH \| National Institute of Allergy and Infectious Diseases (NIAID); R01 AI134696 United States AI NIAID NIH HHS; R21 AI178839 United States AI NIAID NIH HHS; P01AI138949 U.S. Department of Health & Human Services \| NIH \| National Institute of Allergy and Infectious Diseases (NIAID); F31 AI167471 United States AI NIAID NIH HHS; R01AI134696, R01AI116523, R01AI049424, P01AI138949 U.S. Department of Health & Human Services \| NIH \| National Institute of Allergy and Infectious Diseases (NIAID)
تواريخ الأحداث:	Date Created: 20240712 Date Completed: 20240904 Latest Revision: 20240924
رمز التحديث:	20240924
DOI:	10.1038/s41564-024-01756-0
PMID:	38997520
قاعدة البيانات:	MEDLINE

Find this article in full text from Springer Verlag.

Full Text Finder

الوصف
تدمد:	2058-5276
DOI:	10.1038/s41564-024-01756-0