{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T07:26:40Z","timestamp":1792135600828,"version":"4.4.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["SB\/YS\/LS-154\/2013"],"award-info":[{"award-number":["SB\/YS\/LS-154\/2013"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Selective isolation of soil Actinobacteria was undertaken to isolate a new class of antibiotics and bioactive molecules. A <jats:italic>Streptomyces<\/jats:italic> sp<jats:italic>.<\/jats:italic> PSAA01 (=\u2009MTCC 13,157), isolated from soil of Eastern Himalaya foothill was cultivated on a large scale for the production of the antimicrobial SM02. It has been found that the maximum amount of SM02 produced while PSAA01 was grown in ISP-2 medium (pH 7.0) for 7\u00a0days at 30\u00a0\u00b0C in shaking (180\u00a0rpm) condition. A significant zone of inhibition against <jats:italic>Staphylococcus aureus<\/jats:italic> MTCC 96 has been found with the crude cell-free culture media (50 \u00b5L) of 7\u00a0days grown PSAA01. After the purification and chemical structural characterization, we found that SM02 is a new antimicrobial having 746 dalton molecular weight. The compound SM02 contains pyrimidine moiety in it and is produced by a species of <jats:italic>Streptomyces<\/jats:italic> and thus we have named this antibiotic pyrimidomycin<jats:italic>.<\/jats:italic> The antimicrobial spectrum of pyrimidomycin has been found to be restricted in Gram-positive organisms with a MIC of 12\u00a0\u00b5g\/mL. SM02 was found active against <jats:italic>Mycobacterium<\/jats:italic> sp. and also multi-drug resistant Gram-positive bacteria with similar potency and found to disrupt the bacterial cell wall. Pyrimidomycin also showed significant impairment in the biofilm formation by <jats:italic>S. aureus<\/jats:italic>. Furthermore, pyrimidomycin showed synergy with the most used antibiotic like ampicillin, vancomycin and chloramphenicol. Pyrimidomycin did not have cytotoxicity towards human cell lines indicating its limited activity within bacteria.<\/jats:p>","DOI":"10.1038\/s41598-022-14549-4","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T09:10:22Z","timestamp":1655457022000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["An antibacterial compound pyrimidomycin produced by Streptomyces sp. PSAA01 isolated from soil of Eastern Himalayan foothill"],"prefix":"10.1038","volume":"12","author":[{"given":"Prasenjit","family":"Das","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shampa","family":"Kundu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pulak Kumar","family":"Maiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurodeep","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prithidipa","family":"Sahoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukhendu","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"14549_CR1","first-page":"125","volume":"2","author":"RH Baltz","year":"2007","unstructured":"Baltz, R. H. Antimicrobials from actinomycetes: Back to the future. Microbe 2, 125\u2013131 (2007).","journal-title":"Microbe"},{"issue":"3","key":"14549_CR2","doi-asserted-by":"publisher","first-page":"105","DOI":"10.3390\/antibiotics8030105","volume":"8","author":"Y Mast","year":"2019","unstructured":"Mast, Y. & Stegmann, E. Actinomycetes: The antibiotics producers. Antibiotics. 8(3), 105. https:\/\/doi.org\/10.3390\/antibiotics8030105 (2019).","journal-title":"Antibiotics."},{"key":"14549_CR3","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1146\/annurev.mi.37.100183.001201","volume":"37","author":"M Goodfellow","year":"1983","unstructured":"Goodfellow, M. & Williams, S. T. Ecology of actinomycetes. Ann. Rev. Microbiol. 37, 189\u2013216. https:\/\/doi.org\/10.1146\/annurev.mi.37.100183.001201 (1983).","journal-title":"Ann. Rev. Microbiol."},{"key":"14549_CR4","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0378-1119(92)90558-7","volume":"115","author":"AJ McCarthy","year":"1992","unstructured":"McCarthy, A. J. & Williams, S. T. Actinomycetes as agents of biodegradationin the environment\u2014A review. Gene 115, 189\u2013192. https:\/\/doi.org\/10.1016\/0378-1119(92)90558-7 (1992).","journal-title":"Gene"},{"issue":"1","key":"14549_CR5","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.sjbs.2017.05.003","volume":"25","author":"AA Elbendary","year":"2018","unstructured":"Elbendary, A. A. et al. Isolation of antimicrobial producing Actinobacteria from soil samples. Saudi J. Biol. Sci. 25(1), 44\u201346. https:\/\/doi.org\/10.1016\/j.sjbs.2017.05.003 (2018).","journal-title":"Saudi J. Biol. Sci."},{"key":"14549_CR6","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1134\/S0026261707040066","volume":"76","author":"SB Ilic","year":"2007","unstructured":"Ilic, S. B. et al. Characterization and antimicrobial activity of the bioactive metabolites in streptomycete isolates. Microbiology 76, 421\u2013428. https:\/\/doi.org\/10.1134\/S0026261707040066 (2007).","journal-title":"Microbiology"},{"key":"14549_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/MMBR.00019-15","volume":"80","author":"EA Barka","year":"2016","unstructured":"Barka, E. A. et al. Taxonomy, physiology, and natural products of Actinobacteria. Microbiol. Mol. Biol. Rev. 80, 1\u201343. https:\/\/doi.org\/10.1128\/MMBR.00019-15 (2016).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"14549_CR8","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1039\/C7NP00019G","volume":"34","author":"GD Wright","year":"2017","unstructured":"Wright, G. D. Opportunities for natural products in 21st century antibiotic discovery. Nat. Prod. Rep. 34, 694\u2013701. https:\/\/doi.org\/10.1039\/C7NP00019G (2017).","journal-title":"Nat. Prod. Rep."},{"key":"14549_CR9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1093\/bjaceaccp\/mki006","volume":"5","author":"K Inweregbu","year":"2005","unstructured":"Inweregbu, K., Dave, J. & Pittard, A. Nosocomial infections. Contin. Educ. Anaesth. Crit. Care Pain. 5, 14\u201317 (2005).","journal-title":"Contin. Educ. Anaesth. Crit. Care Pain."},{"issue":"5","key":"14549_CR10","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1093\/femsre\/fuz014","volume":"43","author":"M Laws","year":"2019","unstructured":"Laws, M., Shaaban, A. & Rahman, K. M. Antibiotic resistance breakers: Current approaches and future directions. FEMS Microbiol. Rev. 43(5), 490\u2013516. https:\/\/doi.org\/10.1093\/femsre\/fuz014 (2019).","journal-title":"FEMS Microbiol. Rev."},{"key":"14549_CR11","first-page":"167","volume":"3","author":"MP Singh","year":"2000","unstructured":"Singh, M. P. & Greenstein, M. Antibacterial leads from microbial natural products discovery. Curr. Opin. Drug Disc. Develop. 3, 167\u2013176 (2000).","journal-title":"Curr. Opin. Drug Disc. Develop."},{"issue":"1","key":"14549_CR12","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1089\/mdr.2018.0027","volume":"25","author":"V Cepas","year":"2018","unstructured":"Cepas, V. et al. Relationship between biofilm formation and antimicrobial resistance in gram-negative bacteria. Microb. Drug Resist. 25(1), 72\u201379. https:\/\/doi.org\/10.1089\/mdr.2018.0027 (2018).","journal-title":"Microb. Drug Resist."},{"key":"14549_CR13","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/ja.2010.22","volume":"63","author":"N Haste","year":"2010","unstructured":"Haste, N. et al. Activity of the streptogramin antibiotic etamycin against methicillin-resistant Staphylococcus aureus. J. Antibiot. 63, 219\u2013224. https:\/\/doi.org\/10.1038\/ja.2010.22 (2010).","journal-title":"J. Antibiot."},{"issue":"1","key":"14549_CR14","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/ja.2008.16","volume":"62","author":"AL Demain","year":"2009","unstructured":"Demain, A. L. & Sanchez, S. Microbial drug discovery: 80 years of progress. J. Antibiot. 62(1), 5\u201316. https:\/\/doi.org\/10.1038\/ja.2008.16 (2009).","journal-title":"J. Antibiot."},{"issue":"6","key":"14549_CR15","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1016\/j.cell.2014.11.017","volume":"159","author":"H Cho","year":"2014","unstructured":"Cho, H., Uehara, T. & Bernhardt, T. G. Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery. Cell 159(6), 1300\u20131311. https:\/\/doi.org\/10.1016\/j.cell.2014.11.017 (2014).","journal-title":"Cell"},{"issue":"2","key":"14549_CR16","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/0306-9877(95)90085-3","volume":"44","author":"RB Ghooi","year":"1995","unstructured":"Ghooi, R. B. & Thatte, S. M. Inhibition of cell wall synthesis\u2014is this the mechanism of action of penicillins?. Med. Hypotheses 44(2), 127\u2013131. https:\/\/doi.org\/10.1016\/0306-9877(95)90085-3 (1995).","journal-title":"Med. Hypotheses"},{"issue":"1","key":"14549_CR17","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1146\/annurev.me.18.020167.002411","volume":"18","author":"AS Weisberger","year":"1967","unstructured":"Weisberger, A. S. Inhibition of protein synthesis by chloramphenicol. Annu. Rev. Med. 18(1), 483\u2013494. https:\/\/doi.org\/10.1146\/annurev.me.18.020167.002411 (1967).","journal-title":"Annu. Rev. Med."},{"issue":"3","key":"14549_CR18","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1111\/j.1432-1033.1973.tb03020.x","volume":"37","author":"DJW Burns","year":"1973","unstructured":"Burns, D. J. W. & Cundliffe, E. Bacterial-protein synthesis: A novel system for studying antibiotic action in vivo. Eur. J. Biochem. 37(3), 570\u2013574. https:\/\/doi.org\/10.1111\/j.1432-1033.1973.tb03020.x (1973).","journal-title":"Eur. J. Biochem."},{"issue":"3","key":"14549_CR19","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1128\/AAC.29.3.474","volume":"29","author":"J Levy","year":"1986","unstructured":"Levy, J. et al. A Effect of tobramycin on protein synthesis in 2-deoxystreptamine aminoglycoside-resistant clinical isolates of Haemophilus influenzae. Antimicrob. Agents Chemother. 29(3), 474\u2013481. https:\/\/doi.org\/10.1128\/AAC.29.3.474 (1986).","journal-title":"Antimicrob. Agents Chemother."},{"issue":"2","key":"14549_CR20","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1128\/AAC.12.2.163","volume":"12","author":"LE Bryan","year":"1977","unstructured":"Bryan, L. E. & Van Den Elzen, H. M. Effects of membrane-energy mutations and cations on streptomycin and gentamicin accumulation by bacteria: a model for entry of streptomycin and gentamicin in susceptible and resistant bacteria. Antimicrob. Agents Chemother. 12(2), 163\u2013177. https:\/\/doi.org\/10.1128\/AAC.12.2.163 (1977).","journal-title":"Antimicrob. Agents Chemother."},{"issue":"1","key":"14549_CR21","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1146\/annurev.bi.46.070177.003233","volume":"46","author":"NR Cozzarelli","year":"1977","unstructured":"Cozzarelli, N. R. The mechanism of action of inhibitors of DNA synthesis. Annu. Rev. Biochem. 46(1), 641\u2013668. https:\/\/doi.org\/10.1146\/annurev.bi.46.070177.003233 (1977).","journal-title":"Annu. Rev. Biochem."},{"key":"14549_CR22","first-page":"75","volume":"11","author":"MA El-Nakeeb","year":"1963","unstructured":"El-Nakeeb, M. A. & Lechevalier, H. A. Selective isolation of aerobic actinomycetes. ApplMicrobiol 11, 75\u201377 (1963).","journal-title":"ApplMicrobiol"},{"key":"14549_CR23","doi-asserted-by":"publisher","first-page":"001","DOI":"10.4172\/1948-5948.S6-001","volume":"S6","author":"DS Ningthoujam","year":"2011","unstructured":"Ningthoujam, D. S., Sanasam, S. & Nimaichand, S. Studies on bioactive Actinomycetes in a niche biotope, Nambul River in Manipur, India. J. Microbial. Biochem. Technol. S6, 001. https:\/\/doi.org\/10.4172\/1948-5948.S6-001 (2011).","journal-title":"J. Microbial. Biochem. Technol."},{"key":"14549_CR24","doi-asserted-by":"publisher","first-page":"220","DOI":"10.4236\/aim.2019.93016","volume":"9","author":"PK Maiti","year":"2019","unstructured":"Maiti, P. K. & Mandal, S. Majority of actinobacterial strains isolated from Kashmir Himalaya soil are rich source of antimicrobials and industrially important biomolecules. Adv. Microbiol. 9, 220\u2013238. https:\/\/doi.org\/10.4236\/aim.2019.93016 (2019).","journal-title":"Adv. Microbiol."},{"issue":"1","key":"14549_CR25","first-page":"107","volume":"54","author":"L Pine","year":"1959","unstructured":"Pine, L. & Watson, S. J. Evaluation of an isolation and maintenance medium for Actinomyces species and related organisms. J. Lab. Clin. Med. 54(1), 107\u2013114 (1959).","journal-title":"J. Lab. Clin. Med."},{"key":"14549_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-66984-w","volume":"10","author":"P Maiti","year":"2020","unstructured":"Maiti, P. et al. Streptomycessp SM01 isolated from Indian soil produces a novel antibiotic picolinamycin effective against multi drug resistant bacterial strains. Sci. Rep. 10, 1\u201312 (2020).","journal-title":"Sci. Rep."},{"key":"14549_CR27","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1099\/ijsem.0.001755","volume":"67","author":"SH Yoon","year":"2017","unstructured":"Yoon, S. H. et al. Introducing EzBioCloud: A taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies. IJSEM 67, 1613. https:\/\/doi.org\/10.1099\/ijsem.0.001755 (2017).","journal-title":"IJSEM"},{"key":"14549_CR28","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1093\/oxfordjournals.molbev.a040454","volume":"4","author":"N Saitou","year":"1987","unstructured":"Saitou, N. & Nei, M. The neighbor-joining method: A new method for reconstructing phylogenetic trees. Mol. Biol. Evol. 4, 406\u2013425. https:\/\/doi.org\/10.1093\/oxfordjournals.molbev.a040454 (1987).","journal-title":"Mol. Biol. Evol."},{"key":"14549_CR29","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1007\/bf01734359","volume":"17","author":"J Felsenstein","year":"1981","unstructured":"Felsenstein, J. Evolutionary trees from DNA-sequences\u2014a maximum-likelihood approach. J. Mol. Evol. 17, 368\u2013376. https:\/\/doi.org\/10.1007\/bf01734359 (1981).","journal-title":"J. Mol. Evol."},{"key":"14549_CR30","doi-asserted-by":"publisher","first-page":"330","DOI":"10.3181\/00379727-48-13311","volume":"48","author":"JH Mueller","year":"1941","unstructured":"Mueller, J. H. & Hinton, J. A protein-free medium for primary isolation of the Gonococcus and Meningococcus. Proc. Soc. Exp. Biol. Med. 48, 330. https:\/\/doi.org\/10.3181\/00379727-48-13311 (1941).","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"14549_CR31","first-page":"313","volume":"16","author":"EB Shirling","year":"1966","unstructured":"Shirling, E. B. & Gottlieb, D. Methods for characterization of Streptomyces sp.. Int. J. Syst. Evol. Microbiol. 16, 313\u2013340 (1966).","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"14549_CR32","volume-title":"Media for Isolation-Cultivation Identification-Maintenance of Medical Bacteria","author":"JF MacFaddin","year":"1985","unstructured":"MacFaddin, J. F. Media for Isolation-Cultivation Identification-Maintenance of Medical Bacteria Vol. 1 (Williams & Wilkins, 1985)."},{"key":"14549_CR33","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/nprot.2007.521","volume":"3","author":"I Wiegand","year":"2008","unstructured":"Wiegand, I., Hilpert, K. & Hancock, R. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat. Protoc. 3, 163\u2013175. https:\/\/doi.org\/10.1038\/nprot.2007.521 (2008).","journal-title":"Nat. Protoc."},{"key":"14549_CR34","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.micron.2010.05.007","volume":"41","author":"AK Tyagi","year":"2010","unstructured":"Tyagi, A. K. & Malik, A. In situ SEM, TEM and AFM studies of the antimicrobial activity of lemon grass oil in liquid and vapour phase against Candida albicans. Micron 41, 797\u2013805. https:\/\/doi.org\/10.1016\/j.micron.2010.05.007 (2010).","journal-title":"Micron"},{"key":"14549_CR35","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.3791\/2437","volume":"47","author":"GA O'Toole","year":"2011","unstructured":"O\u2019Toole, G. A. Microtiter dish biofilm formation assay. J. Vis. Exp. JoVE. 47, 2437. https:\/\/doi.org\/10.3791\/2437 (2011).","journal-title":"J. Vis. Exp. JoVE."},{"key":"14549_CR36","volume-title":"Cancer Cell Culture. Methods in Molecular Biology (Methods and Protocols)","author":"J van Meerloo","year":"2011","unstructured":"van Meerloo, J., Kaspers, G. J. L. & Cloos, J. Cell sensitivity assays: The MTT assay. In Cancer Cell Culture. Methods in Molecular Biology (Methods and Protocols) Vol. 731 (ed. Cree, I.) (Humana Press, 2011)."},{"key":"14549_CR37","doi-asserted-by":"publisher","first-page":"44419","DOI":"10.1038\/srep44419","volume":"7","author":"D Sinha","year":"2017","unstructured":"Sinha, D. et al. Synergistic efficacy of bisbenzimidazole and carbonyl cyanide 3-chlorophenylhydrazone combination against MDR bacterial strains. Sci. Rep. 7, 44419 (2017).","journal-title":"Sci. Rep."},{"issue":"24","key":"14549_CR38","doi-asserted-by":"publisher","first-page":"8351","DOI":"10.1021\/jo101589h","volume":"75","author":"D Williams","year":"2010","unstructured":"Williams, D., Bradley, G. & Lawton, M. Drying of organic solvents: Quantitative evaluation of the efficiency of several desiccants. J. Org. Chem. 75(24), 8351\u20138354. https:\/\/doi.org\/10.1021\/jo101589h (2010).","journal-title":"J. Org. Chem."},{"key":"14549_CR39","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.jiph.2016.08.007","volume":"10","author":"M Frieri","year":"2017","unstructured":"Frieri, M., Kumar, K. & Boutin, A. Antibiotic resistance. J. Infect. Public Health 10, 369\u2013378 (2017).","journal-title":"J. Infect. Public Health"},{"key":"14549_CR40","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.molmed.2012.03.003","volume":"18","author":"P Nordmann","year":"2012","unstructured":"Nordmann, P., Dortet, L. & Poirel, L. Carbapenem resistance in Enterobacteriaceae: Here is the storm!. Trends Mol. Med. 18, 263\u2013272. https:\/\/doi.org\/10.1016\/j.molmed.2012.03.003 (2012).","journal-title":"Trends Mol. Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-14549-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-14549-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-14549-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T05:23:27Z","timestamp":1669353807000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-14549-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,17]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["14549"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-14549-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,17]]},"assertion":[{"value":"10 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10176"}}