{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T05:58:48Z","timestamp":1793771928793,"version":"4.6.1"},"reference-count":115,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM118159"],"award-info":[{"award-number":["R35GM118159"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AT010014"],"award-info":[{"award-number":["R01AT010014"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["F31DK132941"],"award-info":[{"award-number":["F31DK132941"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI172144"],"award-info":[{"award-number":["R01AI172144"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["RM1GM141649"],"award-info":[{"award-number":["RM1GM141649"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Microbiol"],"DOI":"10.1038\/s41564-026-02299-2","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T09:02:51Z","timestamp":1775466171000},"page":"1387-1409","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A drug\u2013microbiome\u2013drug interaction impacts co-prescribed medications for Parkinson\u2019s disease"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-6961","authenticated-orcid":false,"given":"Andrew A.","family":"Verdegaal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joonseok","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahar","family":"Javdan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruojun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R. W.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6403-5884","authenticated-orcid":false,"given":"Jaime A.","family":"Gonz\u00e1lez-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9604-2912","authenticated-orcid":false,"given":"Mohamed S.","family":"Donia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7583-1242","authenticated-orcid":false,"given":"Jason M.","family":"Crawford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7599-3471","authenticated-orcid":false,"given":"Andrew L.","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"2299_CR1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1517\/14740338.2012.631910","volume":"11","author":"L Magro","year":"2012","unstructured":"Magro, L., Moretti, U. & Leone, R. Epidemiology and characteristics of adverse drug reactions caused by drug\u2013drug interactions. Expert Opin. Drug Saf. 11, 83\u201394 (2012).","journal-title":"Expert Opin. Drug Saf."},{"key":"2299_CR2","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.cger.2012.01.002","volume":"28","author":"BM Shah","year":"2012","unstructured":"Shah, B. M. & Hajjar, E. R. Polypharmacy, adverse drug reactions, and geriatric syndromes. Clin. Geriatr. Med. 28, 173\u2013186 (2012).","journal-title":"Clin. Geriatr. Med."},{"key":"2299_CR3","doi-asserted-by":"publisher","first-page":"eadg8357","DOI":"10.1126\/scitranslmed.adg8357","volume":"16","author":"AA Verdegaal","year":"2024","unstructured":"Verdegaal, A. A. & Goodman, A. L. Integrating the gut microbiome and pharmacology. Sci. Transl. Med. 16, eadg8357 (2024).","journal-title":"Sci. Transl. Med."},{"key":"2299_CR4","doi-asserted-by":"publisher","DOI":"10.1126\/science.aag2770","volume":"356","author":"N Koppel","year":"2017","unstructured":"Koppel, N., Maini Rekdal, V. & Balskus, E. P. Chemical transformation of xenobiotics by the human gut microbiota. Science 356, eaag2770 (2017).","journal-title":"Science"},{"key":"2299_CR5","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6323","volume":"364","author":"VM Rekdal","year":"2019","unstructured":"Rekdal, V. M., Bess, E. N., Bisanz, J. E., Turnbaugh, P. J. & Balskus, E. P. Discovery and inhibition of an interspecies gut bacterial pathway for levodopa metabolism. Science 364, eaau6323 (2019).","journal-title":"Science"},{"key":"2299_CR6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08294-y","volume":"10","author":"Kessel","year":"2019","unstructured":"Kessel et al. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson\u2019s disease. Nat. Commun. 10, 310 (2019).","journal-title":"Nat. Commun."},{"key":"2299_CR7","doi-asserted-by":"publisher","first-page":"e2443","DOI":"10.1212\/WNL.0000000000201204","volume":"99","author":"Y Zhang","year":"2022","unstructured":"Zhang, Y. et al. Association between microbial tyrosine decarboxylase gene and levodopa responsiveness in patients with Parkinson disease. Neurology 99, e2443\u2013e2453 (2022).","journal-title":"Neurology"},{"key":"2299_CR8","doi-asserted-by":"publisher","first-page":"7374","DOI":"10.1073\/pnas.1918095117","volume":"117","author":"AP Bhatt","year":"2020","unstructured":"Bhatt, A. P. et al. Targeted inhibition of gut bacterial \u03b2-glucuronidase activity enhances anticancer drug efficacy. Proc. Natl Acad. Sci. USA 117, 7374\u20137381 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2299_CR9","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.chom.2020.12.008","volume":"29","author":"RR Nayak","year":"2021","unstructured":"Nayak, R. R. et al. Methotrexate impacts conserved pathways in diverse human gut bacteria leading to decreased host immune activation. Cell Host Microb. 29, 362\u2013377.e11 (2021).","journal-title":"Cell Host Microb."},{"key":"2299_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-020-00876-3","volume":"18","author":"SP van Kessel","year":"2020","unstructured":"van Kessel, S. P. et al. Gut bacterial deamination of residual levodopa medication for Parkinson\u2019s disease. BMC Biol. 18, 137 (2020).","journal-title":"BMC Biol."},{"key":"2299_CR11","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat9931","volume":"363","author":"M Zimmermann","year":"2019","unstructured":"Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R. & Goodman, A. L. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science 363, eaat9931 (2019).","journal-title":"Science"},{"key":"2299_CR12","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1126\/science.1191175","volume":"330","author":"BD Wallace","year":"2010","unstructured":"Wallace, B. D. et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330, 831\u2013835 (2010).","journal-title":"Science"},{"key":"2299_CR13","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax2358","volume":"5","author":"MR Taylor","year":"2019","unstructured":"Taylor, M. R. et al. Vancomycin relieves mycophenolate mofetil-induced gastrointestinal toxicity by eliminating gut bacterial \u03b2-glucuronidase activity. Sci. Adv. 5, eaax2358 (2019).","journal-title":"Sci. Adv."},{"key":"2299_CR14","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1016\/j.cell.2020.05.001","volume":"181","author":"B Javdan","year":"2020","unstructured":"Javdan, B. et al. Personalized mapping of drug metabolism by the human gut microbiome. Cell 181, 1661\u20131679.e22 (2020).","journal-title":"Cell"},{"key":"2299_CR15","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1038\/s41586-019-1291-3","volume":"570","author":"M Zimmermann","year":"2019","unstructured":"Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R. & Goodman, A. L. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 570, 462\u2013467 (2019).","journal-title":"Nature"},{"key":"2299_CR16","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","volume":"18","author":"VL Feigin","year":"2019","unstructured":"Feigin, V. L. et al. Global, regional, and national burden of neurological disorders, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 18, 459\u2013480 (2019).","journal-title":"Lancet Neurol."},{"key":"2299_CR17","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","volume":"397","author":"BR Bloem","year":"2021","unstructured":"Bloem, B. R., Okun, M. S. & Klein, C. Parkinson\u2019s disease. Lancet 397, 2284\u20132303 (2021).","journal-title":"Lancet"},{"key":"2299_CR18","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1111\/j.1468-1331.2009.02697.x","volume":"16","author":"AHV Schapira","year":"2009","unstructured":"Schapira, A. H. V., Emre, M., Jenner, P. & Poewe, W. Levodopa in the treatment of Parkinson\u2019s disease. Eur. J. Neurol. 16, 982\u2013989 (2009).","journal-title":"Eur. J. Neurol."},{"key":"2299_CR19","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41531-022-00321-y","volume":"8","author":"M Beckers","year":"2022","unstructured":"Beckers, M., Bloem, B. R. & Verbeek, M. M. Mechanisms of peripheral levodopa resistance in Parkinson\u2019s disease. npj Parkinsons Dis. 8, 56 (2022).","journal-title":"npj Parkinsons Dis."},{"key":"2299_CR20","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/clpt.1980.161","volume":"28","author":"DK Reilly","year":"1980","unstructured":"Reilly, D. K., Rivera-Calimlim, L. & Van Dyke, D. Catechol-O-methyltransferase activity: a determinant of levodopa response. Clin. Pharmacol. Ther. 28, 278\u2013286 (1980).","journal-title":"Clin. Pharmacol. Ther."},{"key":"2299_CR21","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1111\/j.1527-3458.2007.00020.x","volume":"13","author":"MJ Bonif\u00e1cio","year":"2007","unstructured":"Bonif\u00e1cio, M. J., Palma, P. N., Almeida, L. & Soares-da-Silva, P. Catechol-O-methyltransferase and its inhibitors in Parkinson\u2019s disease. CNS Drug Rev. 13, 352\u2013379 (2007).","journal-title":"CNS Drug Rev."},{"key":"2299_CR22","doi-asserted-by":"publisher","first-page":"93","DOI":"10.4315\/0362-028X-71.1.93","volume":"71","author":"S Torriani","year":"2008","unstructured":"Torriani, S. et al. Rapid detection and quantification of tyrosine decarboxylase gene (tdc) and its expression in Gram-positive bacteria associated with fermented foods using PCR-based methods. J. Food Prot. 71, 93\u2013101 (2008).","journal-title":"J. Food Prot."},{"key":"2299_CR23","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41531-025-00903-6","volume":"11","author":"N Miyaue","year":"2025","unstructured":"Miyaue, N. et al. Association of Enterococcus faecalis and tyrosine decarboxylase gene levels with levodopa pharmacokinetics in Parkinson\u2019s disease. npj Parkinsons Dis. 11, 49 (2025).","journal-title":"npj Parkinsons Dis."},{"key":"2299_CR24","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.parkreldis.2019.06.003","volume":"65","author":"D Pietrucci","year":"2019","unstructured":"Pietrucci, D. et al. Dysbiosis of gut microbiota in a selected population of Parkinson\u2019s patients. Parkinsonism Relat. Disord. 65, 124\u2013130 (2019).","journal-title":"Parkinsonism Relat. Disord."},{"key":"2299_CR25","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/s41531-019-0100-x","volume":"5","author":"S Weis","year":"2019","unstructured":"Weis, S. et al. Effect of Parkinson\u2019s disease and related medications on the composition of the fecal bacterial microbiota. npj Parkinsons Dis. 5, 28 (2019).","journal-title":"npj Parkinsons Dis."},{"key":"2299_CR26","doi-asserted-by":"crossref","unstructured":"van Kessel, S. P., Auvinen, P., Scheperjans, F. & El Aidy, S. Gut bacterial tyrosine decarboxylase associates with clinical variables in a longitudinal cohort study of Parkinsons disease. NPJ Parkinsons Dis. 7, 115, 1\u20138 (2021).","DOI":"10.1038\/s41531-021-00260-0"},{"key":"2299_CR27","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nature25979","volume":"555","author":"L Maier","year":"2018","unstructured":"Maier, L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555, 623\u2013628 (2018).","journal-title":"Nature"},{"key":"2299_CR28","doi-asserted-by":"publisher","first-page":"e1000423","DOI":"10.1371\/journal.pcbi.1000423","volume":"5","author":"SL Kinnings","year":"2009","unstructured":"Kinnings, S. L. et al. Drug discovery using chemical systems biology: repositioning the safe medicine comtan to treat multi-drug and extensively drug resistant tuberculosis. PLoS Comput. Biol. 5, e1000423 (2009).","journal-title":"PLoS Comput. Biol."},{"key":"2299_CR29","doi-asserted-by":"publisher","first-page":"3165","DOI":"10.1038\/s41564-024-01853-0","volume":"9","author":"FC Pereira","year":"2024","unstructured":"Pereira, F. C. et al. The Parkinson\u2019s disease drug entacapone disrupts gut microbiome homoeostasis via iron sequestration. Nat. Microbiol. 9, 3165\u20133183 (2024).","journal-title":"Nat. Microbiol."},{"key":"2299_CR30","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1021\/js960458s","volume":"86","author":"M Orama","year":"1997","unstructured":"Orama, M., Tilus, P., Taskinen, J. & Lotta, T. Iron(III)-chelating properties of the novel catechol O-methyltransferase inhibitor entacapone in aqueous solution. J. Pharm. Sci. 86, 827\u2013831 (1997).","journal-title":"J. Pharm. Sci."},{"key":"2299_CR31","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1016\/S0021-9258(19)41759-6","volume":"250","author":"CA Tyson","year":"1975","unstructured":"Tyson, C. A. 4-Nitrocatechol as a colorimetric probe for non-heme iron dioxygenases. J. Biol. Chem. 250, 1765\u20131770 (1975).","journal-title":"J. Biol. Chem."},{"key":"2299_CR32","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1046\/j.1365-2125.1999.00036.x","volume":"48","author":"K Jorga","year":"1999","unstructured":"Jorga, K., Fotteler, B., Heizmann, P. & Gasser, R. Metabolism and excretion of tolcapone, a novel inhibitor of catechol-O-methyltransferase. Br. J. Clin. Pharmacol. 48, 513\u2013520 (1999).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"2299_CR33","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.chembiol.2016.11.011","volume":"24","author":"G Cox","year":"2017","unstructured":"Cox, G. et al. A common platform for antibiotic dereplication and adjuvant discovery. Cell Chem. Biol. 24, 98\u2013109 (2017).","journal-title":"Cell Chem. Biol."},{"key":"2299_CR34","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/S0277-5387(00)86923-5","volume":"11","author":"M Aplincourt","year":"1992","unstructured":"Aplincourt, M. et al. Metal cation\u2013ligand interactions of catechols of biological importance\u2014I. Stability of iron(III) dihydroxybenzamide complexes which are related to cephalosporins bearing at C3\u2032 a catechol group. Polyhedron 11, 1161\u20131168 (1992).","journal-title":"Polyhedron"},{"key":"2299_CR35","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1016\/0006-2952(96)00101-3","volume":"51","author":"T Kawabata","year":"1996","unstructured":"Kawabata, T., Schepkin, V., Haramaki, N., Phadke, R. S. & Packer, L. Iron coordination by catechol derivative antioxidants. Biochem. Pharmacol. 51, 1569\u20131577 (1996).","journal-title":"Biochem. Pharmacol."},{"key":"2299_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5910","volume":"5","author":"SW Seo","year":"2014","unstructured":"Seo, S. W. et al. Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli. Nat. Commun. 5, 4910 (2014).","journal-title":"Nat. Commun."},{"key":"2299_CR37","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.04733-22","volume":"11","author":"JP Lewis","year":"2023","unstructured":"Lewis, J. P. & Gui, Q. Iron deficiency modulates metabolic landscape of Bacteroidetes promoting its resilience during inflammation. Microbiol. Spectr. 11, e04733-22 (2023).","journal-title":"Microbiol. Spectr."},{"key":"2299_CR38","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/255498a0","volume":"255","author":"RL Willson","year":"1975","unstructured":"Willson, R. L. & Searle, A. J. F. Metronidazole (Flagyl): iron catalysed reaction with sulphydryl groups and tumour radiosensitisation. Nature 255, 498\u2013500 (1975).","journal-title":"Nature"},{"key":"2299_CR39","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1111\/j.1574-6968.1991.tb04567.x","volume":"84","author":"ER Rocha","year":"1991","unstructured":"Rocha, E. R., de Uzeda, M. & Brock, J. H. Effect of ferric and ferrous iron chelators on growth of Bacteroides fragilis under anaerobic conditions. FEMS Microbiol. Lett. 84, 45\u201350 (1991).","journal-title":"FEMS Microbiol. Lett."},{"key":"2299_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.101808","volume":"298","author":"AE Sestok","year":"2022","unstructured":"Sestok, A. E. et al. A fusion of the Bacteroides fragilis ferrous iron import proteins reveals a role for FeoA in stabilizing GTP-bound FeoB. J. Biol. Chem. 298, 101808 (2022).","journal-title":"J. Biol. Chem."},{"key":"2299_CR41","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1111\/j.1574-6968.1981.tb07606.x","volume":"12","author":"K Hantke","year":"1981","unstructured":"Hantke, K. & Zimmermann, L. The importance of the exbB gene for vitamin B12 and ferric iron transport. FEMS Microbiol. Lett. 12, 31\u201335 (1981).","journal-title":"FEMS Microbiol. Lett."},{"key":"2299_CR42","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1046\/j.1365-2958.2002.02880.x","volume":"44","author":"PI Higgs","year":"2002","unstructured":"Higgs, P. I., Larsen, R. A. & Postle, K. Quantification of known components of the Escherichia coli TonB energy transduction system: TonB, ExbB, ExbD and FepA. Mol. Microbiol. 44, 271\u2013281 (2002).","journal-title":"Mol. Microbiol."},{"key":"2299_CR43","doi-asserted-by":"publisher","first-page":"10951","DOI":"10.1021\/bi201517h","volume":"50","author":"M Miethke","year":"2011","unstructured":"Miethke, M., Hou, J. & Marahiel, M. A. The siderophore-interacting protein YqjH acts as a ferric reductase in different iron assimilation pathways of Escherichia coli. Biochemistry 50, 10951\u201310964 (2011).","journal-title":"Biochemistry"},{"key":"2299_CR44","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.898453","volume":"13","author":"A Paunkov","year":"2022","unstructured":"Paunkov, A., S\u00f3ki, J. & Leitsch, D. Modulation of iron import and metronidazole resistance in Bacteroides fragilis harboring a nimA gene. Front. Microbiol. 13, 898453 (2022).","journal-title":"Front. Microbiol."},{"key":"2299_CR45","doi-asserted-by":"publisher","unstructured":"Deshpande, A., Wu, X., Huo, W., Palmer, K. L. & Hurdle, J. G. Chromosomal resistance to metronidazole in Clostridioides difficile can be mediated by epistasis between iron homeostasis and oxidoreductases. Antimicrob. Agents Chemother. https:\/\/doi.org\/10.1128\/aac.00415-20 (2020).","DOI":"10.1128\/aac.00415-20"},{"key":"2299_CR46","doi-asserted-by":"publisher","first-page":"2634","DOI":"10.1093\/jac\/dku219","volume":"69","author":"Y Veeranagouda","year":"2014","unstructured":"Veeranagouda, Y. et al. Deficiency of the ferrous iron transporter FeoAB is linked with metronidazole resistance in Bacteroides fragilis. J. Antimicrob. Chemother. 69, 2634\u20132643 (2014).","journal-title":"J. Antimicrob. Chemother."},{"key":"2299_CR47","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.resmic.2010.04.003","volume":"161","author":"LS Steffens","year":"2010","unstructured":"Steffens, L. S. et al. Bacteroides fragilis RecA protein overexpression causes resistance to metronidazole. Res. Microbiol. 161, 346\u2013354 (2010).","journal-title":"Res. Microbiol."},{"key":"2299_CR48","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/0006-2952(94)90144-9","volume":"48","author":"JH Tocher","year":"1994","unstructured":"Tocher, J. H. & Edwards, D. I. Evidence for the direct interaction of reduced metronidazole derivatives with DNA bases. Biochem. Pharmacol. 48, 1089\u20131094 (1994).","journal-title":"Biochem. Pharmacol."},{"key":"2299_CR49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2024.100566","volume":"26","author":"A-L Mayr","year":"2024","unstructured":"Mayr, A.-L., Paunkov, A., Hummel, K., Razzazi-Fazeli, E. & Leitsch, D. Comparative proteomic analysis of metronidazole-sensitive and resistant Trichomonas vaginalis suggests a novel mode of metronidazole action and resistance. Int. J. Parasitol. Drugs Drug Resist. 26, 100566 (2024).","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"2299_CR50","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01465","volume":"7","author":"MCR de Freitas","year":"2016","unstructured":"de Freitas, M. C. R. et al. Exploratory investigation of Bacteroides fragilis transcriptional response during in vitro exposure to subinhibitory concentration of metronidazole. Front. Microbiol. 7, 1465 (2016).","journal-title":"Front. Microbiol."},{"key":"2299_CR51","doi-asserted-by":"publisher","first-page":"14488","DOI":"10.1074\/jbc.RA119.012300","volume":"295","author":"W He","year":"2020","unstructured":"He, W. et al. Increased surface charge in the protein chaperone Spy enhances its anti-aggregation activity. J. Biol. Chem. 295, 14488\u201314500 (2020).","journal-title":"J. Biol. Chem."},{"key":"2299_CR52","doi-asserted-by":"publisher","first-page":"4971","DOI":"10.1016\/j.jmb.2018.10.021","volume":"430","author":"K Rome","year":"2018","unstructured":"Rome, K. et al. The two-component system ZraPSR is a novel ESR that contributes to intrinsic antibiotic tolerance in Escherichia coli. J. Mol. Biol. 430, 4971\u20134985 (2018).","journal-title":"J. Mol. Biol."},{"key":"2299_CR53","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1099\/00221287-148-6-1757","volume":"148","author":"D Kuczynska-Wisnik","year":"2002","unstructured":"Kuczynska-Wisnik, D. et al. The Escherichia coli small heat-shock proteins IbpA and IbpB prevent the aggregation of endogenous proteins denatured in vivo during extreme heat shock. Microbiology 148, 1757\u20131765 (2002).","journal-title":"Microbiology"},{"key":"2299_CR54","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1002\/mds.26942","volume":"32","author":"EM Hill-Burns","year":"2017","unstructured":"Hill-Burns, E. M. et al. Parkinson\u2019s disease and Parkinson\u2019s disease medications have distinct signatures of the gut microbiome. Mov. Disord. 32, 739\u2013749 (2017).","journal-title":"Mov. Disord."},{"key":"2299_CR55","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.837019","volume":"12","author":"S-C Fu","year":"2022","unstructured":"Fu, S.-C. et al. A pilot study exploring the association of entacapone, gut microbiota, and the subsequent side effects in patients with Parkinson\u2019s disease. Front. Cell. Infect. Microbiol. 12, 837019 (2022).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"2299_CR56","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1097\/00002826-198403000-00002","volume":"7","author":"JG Nutl","year":"1984","unstructured":"Nutl, J. G. & Fellman, J. H. Pharmacokinetics of levodopa. Clin. Neuropharmacol. 7, 35\u201350 (1984).","journal-title":"Clin. Neuropharmacol."},{"key":"2299_CR57","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/j.cell.2017.04.027","volume":"169","author":"F Lebreton","year":"2017","unstructured":"Lebreton, F. et al. Tracing the enterococci from Paleozoic origins to the hospital. Cell 169, 849\u2013861.e13 (2017).","journal-title":"Cell"},{"key":"2299_CR58","unstructured":"RYTARY (Carbidopa and Levodopa) Full Prescribing Information Reference ID: 3680199 (Impax Laboratories, Inc., 2015); https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/203312s000lbl.pdf"},{"key":"2299_CR59","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1016\/j.chom.2024.10.002","volume":"32","author":"M Bae","year":"2024","unstructured":"Bae, M. et al. Metatranscriptomics-guided discovery and characterization of a polyphenol-metabolizing gut microbial enzyme. Cell Host Microbe 32, 1887\u20131896.e8 (2024).","journal-title":"Cell Host Microbe"},{"key":"2299_CR60","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1002\/mnfr.200800446","volume":"53","author":"M Larrosa","year":"2009","unstructured":"Larrosa, M. et al. Polyphenol metabolites from colonic microbiota exert anti-inflammatory activity on different inflammation models. Mol. Nutr. Food Res. 53, 1044\u20131054 (2009).","journal-title":"Mol. Nutr. Food Res."},{"key":"2299_CR61","doi-asserted-by":"publisher","unstructured":"Fahn, S. in Drugs for the Treatment of Parkinson\u2019s Disease (ed. Calne, D. B.) 385\u2013409 (Springer, 1989); https:\/\/doi.org\/10.1007\/978-3-642-73899-9_14","DOI":"10.1007\/978-3-642-73899-9_14"},{"key":"2299_CR62","doi-asserted-by":"publisher","first-page":"S497","DOI":"10.1002\/mds.22028","volume":"23","author":"S Fahn","year":"2008","unstructured":"Fahn, S. The history of dopamine and levodopa in the treatment of Parkinson\u2019s disease. Mov. Disord. 23, S497\u2013S508 (2008).","journal-title":"Mov. Disord."},{"key":"2299_CR63","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.chom.2009.08.003","volume":"6","author":"AL Goodman","year":"2009","unstructured":"Goodman, A. L. et al. Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe 6, 279\u2013289 (2009).","journal-title":"Cell Host Microbe"},{"key":"2299_CR64","doi-asserted-by":"publisher","first-page":"6327","DOI":"10.1016\/j.cell.2024.08.038","volume":"187","author":"EJ Culp","year":"2024","unstructured":"Culp, E. J., Nelson, N. T., Verdegaal, A. A. & Goodman, A. L. Microbial transformation of dietary xenobiotics shapes gut microbiome composition. Cell 187, 6327\u20136345.e20 (2024).","journal-title":"Cell"},{"key":"2299_CR65","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1093\/ijnp\/pyac021","volume":"25","author":"S Habet","year":"2022","unstructured":"Habet, S. Clinical pharmacology of entacapone (Comtan) trom the FDA reviewer. Int. J. Neuropsychopharmacol. 25, 567\u2013575 (2022).","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"2299_CR66","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S0090-9556(25)07341-6","volume":"21","author":"T Wikberg","year":"1993","unstructured":"Wikberg, T., Vuorela, A., Ottoila, P. & Taskinen, J. Identification of major metabolites of the catechol-O-methyltransferase inhibitor entacapone in rats and humans. Drug Metab. Dispos. 21, 81\u201392 (1993).","journal-title":"Drug Metab. Dispos."},{"key":"2299_CR67","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1016\/S0090-9556(24)15088-X","volume":"28","author":"P Lautala","year":"2000","unstructured":"Lautala, P., Ethell, B. T., Taskinen, J. & Burchell, B. The specificity of glucuronidation of entacapone and tolcapone by recombinant human Udp-glucuronosyltransferases. Drug Metab. Dispos. 28, 1385\u20131389 (2000).","journal-title":"Drug Metab. Dispos."},{"key":"2299_CR68","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1007\/s002280000244","volume":"56","author":"H Heikkinen","year":"2001","unstructured":"Heikkinen, H., Saraheimo, M., Antila, S., Ottoila, P. & Pentik\u00e4inen, P. J. Pharmacokinetics of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, in man. Eur. J. Clin. Pharmacol. 56, 821\u2013826 (2001).","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"2299_CR69","doi-asserted-by":"publisher","first-page":"101543","DOI":"10.1016\/j.mex.2021.101543","volume":"8","author":"P Bellio","year":"2021","unstructured":"Bellio, P., Fagnani, L., Nazzicone, L. & Celenza, G. New and simplified method for drug combination studies by checkerboard assay. MethodsX 8, 101543 (2021).","journal-title":"MethodsX"},{"key":"2299_CR70","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/s41587-019-0036-z","volume":"37","author":"JJ Almagro Armenteros","year":"2019","unstructured":"Almagro Armenteros, J. J. et al. SignalP 5.0 improves signal peptide predictions using deep neural networks. Nat. Biotechnol. 37, 420\u2013423 (2019).","journal-title":"Nat. Biotechnol."},{"key":"2299_CR71","doi-asserted-by":"publisher","DOI":"10.1038\/msb4100050","volume":"2","author":"T Baba","year":"2006","unstructured":"Baba, T. et al. Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection. Mol. Syst. Biol. 2, 2006.0008 (2006).","journal-title":"Mol. Syst. Biol."},{"key":"2299_CR72","doi-asserted-by":"publisher","first-page":"1.17.1","DOI":"10.1002\/0471142727.mb0117s79","volume":"79","author":"LC Thomason","year":"2007","unstructured":"Thomason, L. C., Costantino, N. & Court, D. L. E. coli genome manipulation by P1 transduction. Curr. Protoc. Mol. Biol. 79, 1.17.1\u20131.17.8 (2007).","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"2299_CR73","doi-asserted-by":"publisher","first-page":"3139","DOI":"10.1016\/j.celrep.2020.02.033","volume":"30","author":"F Stirling","year":"2020","unstructured":"Stirling, F. et al. Synthetic cassettes for pH-mediated sensing, counting, and containment. Cell Rep. 30, 3139\u20133148.e4 (2020).","journal-title":"Cell Rep."},{"key":"2299_CR74","doi-asserted-by":"publisher","unstructured":"Gonzales, M. F., Brooks, T., Pukatzki, S. U. & Provenzano, D. Rapid protocol for preparation of electrocompetent Escherichia coli and Vibrio cholerae. J. Vis. Exp. https:\/\/doi.org\/10.3791\/50684 (2013).","DOI":"10.3791\/50684"},{"key":"2299_CR75","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/0378-1119(95)00193-A","volume":"158","author":"PP Cherepanov","year":"1995","unstructured":"Cherepanov, P. P. & Wackernagel, W. Gene disruption in Escherichia coli: TcR and KmR cassettes with the option of Flp-catalyzed excision of the antibiotic-resistance determinant. Gene 158, 9\u201314 (1995).","journal-title":"Gene"},{"key":"2299_CR76","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.cell.2017.03.045","volume":"169","author":"B Lim","year":"2017","unstructured":"Lim, B., Zimmermann, M., Barry, N. A. & Goodman, A. L. Engineered regulatory systems modulate gene expression of human commensals in the gut. Cell 169, 547\u2013558.e15 (2017).","journal-title":"Cell"},{"key":"2299_CR77","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.chom.2008.09.007","volume":"4","author":"EC Martens","year":"2008","unstructured":"Martens, E. C., Chiang, H. C. & Gordon, J. I. Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont. Cell Host Microbe 4, 447\u2013457 (2008).","journal-title":"Cell Host Microbe"},{"key":"2299_CR78","doi-asserted-by":"publisher","first-page":"D444","DOI":"10.1093\/nar\/gkae1082","volume":"53","author":"M Blum","year":"2024","unstructured":"Blum, M. et al. InterPro: the protein sequence classification resource in 2025. Nucleic Acids Res. 53, D444\u2013D456 (2024).","journal-title":"Nucleic Acids Res."},{"key":"2299_CR79","unstructured":"Wilkins, D. gggenes: draw gene arrow maps in \u2018Ggplot2\u2019. Version: 0.5.1 https:\/\/wilkox.org\/gggenes\/ (2020)."},{"key":"2299_CR80","doi-asserted-by":"crossref","unstructured":"Wickham, H. ggplot2: Elegant Graphics for Data Analysis. Version: 3.5.2 (Springer, 2016).","DOI":"10.1007\/978-3-319-24277-4"},{"key":"2299_CR81","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.watres.2004.11.011","volume":"39","author":"RA Haugland","year":"2005","unstructured":"Haugland, R. A., Siefring, S. C., Wymer, L. J., Brenner, K. P. & Dufour, A. P. Comparison of Enterococcus measurements in freshwater at two recreational beaches by quantitative polymerase chain reaction and membrane filter culture analysis. Water Res. 39, 559\u2013568 (2005).","journal-title":"Water Res."},{"key":"2299_CR82","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1002\/hep4.1740","volume":"5","author":"K Yan","year":"2021","unstructured":"Yan, K. et al. Obeticholic acid decreases intestinal content of Enterococcus in rats with cirrhosis and ascites. Hepatol. Commun. 5, 1507\u20131517 (2021).","journal-title":"Hepatol. Commun."},{"key":"2299_CR83","doi-asserted-by":"publisher","first-page":"5112","DOI":"10.1128\/AEM.01043-13","volume":"79","author":"JJ Kozich","year":"2013","unstructured":"Kozich, J. J., Westcott, S. L., Baxter, N. T., Highlander, S. K. & Schloss, P. D. Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform. Appl. Environ. Microbiol. 79, 5112\u20135120 (2013).","journal-title":"Appl. Environ. Microbiol."},{"key":"2299_CR84","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","volume":"37","author":"E Bolyen","year":"2019","unstructured":"Bolyen, E. et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat. Biotechnol. 37, 852\u2013857 (2019).","journal-title":"Nat. Biotechnol."},{"key":"2299_CR85","doi-asserted-by":"publisher","DOI":"10.1186\/2047-217X-1-7","volume":"1","author":"D McDonald","year":"2012","unstructured":"McDonald, D. et al. The Biological Observation Matrix (BIOM) format or: how I learned to stop worrying and love the ome-ome. Gigascience 1, 7 (2012).","journal-title":"Gigascience"},{"key":"2299_CR86","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nmeth.1184","volume":"5","author":"M Hamady","year":"2008","unstructured":"Hamady, M., Walker, J. J., Harris, J. K., Gold, N. J. & Knight, R. Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex. Nat. Methods 5, 235\u2013237 (2008).","journal-title":"Nat. Methods"},{"key":"2299_CR87","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","volume":"13","author":"BJ Callahan","year":"2016","unstructured":"Callahan, B. J. et al. DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581\u2013583 (2016).","journal-title":"Nat. Methods"},{"key":"2299_CR88","unstructured":"Bisanz, J. E. qiime2R: Importing QIIME2 artifacts and associated data into R sessions. Version: 0.99.6 https:\/\/github.com\/jbisanz\/qiime2R (2018)."},{"key":"2299_CR89","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1111\/2041-210X.12569","volume":"7","author":"LM Hallett","year":"2016","unstructured":"Hallett, L. M. et al. CODYN: an R package of community dynamics metrics. Methods Ecol. Evol. 7, 1146\u20131151 (2016).","journal-title":"Methods Ecol. Evol."},{"key":"2299_CR90","doi-asserted-by":"publisher","DOI":"10.1002\/ecs2.2881","volume":"10","author":"ML Avolio","year":"2019","unstructured":"Avolio, M. L. et al. A comprehensive approach to analyzing community dynamics using rank abundance curves. Ecosphere 10, e02881 (2019).","journal-title":"Ecosphere"},{"key":"2299_CR91","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1111\/j.1654-1103.2003.tb02228.x","volume":"14","author":"P Dixon","year":"2003","unstructured":"Dixon, P. VEGAN, a package of R functions for community ecology. J. Veg. Sci. 14, 927\u2013930 (2003).","journal-title":"J. Veg. Sci."},{"key":"2299_CR92","unstructured":"Morpheus. https:\/\/software.broadinstitute.org\/morpheus\/ (2026)."},{"key":"2299_CR93","doi-asserted-by":"publisher","DOI":"10.1016\/j.lwt.2022.113769","volume":"166","author":"E Kim","year":"2022","unstructured":"Kim, E., Kim, D.-S., Yang, S.-M. & Kim, H.-Y. The accurate identification and quantification of six Enterococcus species using quantitative polymerase chain reaction based novel DNA markers. LWT 166, 113769 (2022).","journal-title":"LWT"},{"key":"2299_CR94","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.chom.2016.12.008","volume":"21","author":"T Miki","year":"2017","unstructured":"Miki, T., Goto, R., Fujimoto, M., Okada, N. & Hardt, W.-D. The bactericidal lectin RegIII\u03b2 prolongs gut colonization and enteropathy in the streptomycin mouse model for Salmonella diarrhea. Cell Host Microbe 21, 195\u2013207 (2017).","journal-title":"Cell Host Microbe"},{"key":"2299_CR95","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/nature14098","volume":"517","author":"LL Ling","year":"2015","unstructured":"Ling, L. L. et al. A new antibiotic kills pathogens without detectable resistance. Nature 517, 455\u2013459 (2015).","journal-title":"Nature"},{"key":"2299_CR96","doi-asserted-by":"publisher","first-page":"e01207","DOI":"10.1128\/AAC.01207-19","volume":"64","author":"A O\u2019Rourke","year":"2020","unstructured":"O\u2019Rourke, A. et al. Mechanism-of-action classification of antibiotics by global transcriptome profiling. Antimicrob. Agents Chemother. 64, e01207\u2013e01219 (2020).","journal-title":"Antimicrob. Agents Chemother."},{"key":"2299_CR97","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357\u2013359 (2012).","journal-title":"Nat. Methods"},{"key":"2299_CR98","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. et al. The Sequence Alignment\/Map format and SAMtools. Bioinformatics 25, 2078\u20132079 (2009).","journal-title":"Bioinformatics"},{"key":"2299_CR99","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"2299_CR100","unstructured":"The UniProt Consortium UniProt: the universal protein knowledgebase in 2025. Nucleic Acids Res. 53, D609\u2013D617 (2025)."},{"key":"2299_CR101","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1093\/bib\/bbx085","volume":"20","author":"PD Karp","year":"2019","unstructured":"Karp, P. D. et al. The BioCyc collection of microbial genomes and metabolic pathways. Brief. Bioinform. 20, 1085\u20131093 (2019).","journal-title":"Brief. Bioinform."},{"key":"2299_CR102","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/nature22308","volume":"545","author":"MF Richter","year":"2017","unstructured":"Richter, M. F. et al. Predictive compound accumulation rules yield a broad-spectrum antibiotic. Nature 545, 299\u2013304 (2017).","journal-title":"Nature"},{"key":"2299_CR103","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1021\/tx025569n","volume":"16","author":"KS Smith","year":"2003","unstructured":"Smith, K. S. et al. In vitro metabolism of tolcapone to reactive intermediates: relevance to tolcapone liver toxicity. Chem. Res. Toxicol. 16, 123\u2013128 (2003).","journal-title":"Chem. Res. Toxicol."},{"key":"2299_CR104","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1038\/s41557-025-01789-w","volume":"17","author":"Q Wu","year":"2025","unstructured":"Wu, Q. et al. Activity of GPCR-targeted drugs influenced by human gut microbiota metabolism. Nat. Chem 17, 808\u2013821 (2025).","journal-title":"Nat. Chem"},{"key":"2299_CR105","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.yrtph.2004.03.001","volume":"39","author":"K Schneider","year":"2004","unstructured":"Schneider, K., Oltmanns, J. & Hassauer, M. Allometric principles for interspecies extrapolation in toxicological risk assessment\u2014empirical investigations. Regul. Toxicol. Pharmacol. 39, 334\u2013347 (2004).","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"2299_CR106","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1021\/js960440h","volume":"86","author":"TH Lave","year":"1997","unstructured":"Lave, T. H. et al. Integration of in vitro data into allometric scaling to predict hepatic metabolic clearance in man: application to 10 extensively metabolized drugs. J. Pharm. Sci. 86, 584\u2013590 (1997).","journal-title":"J. Pharm. Sci."},{"key":"2299_CR107","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/0976-0105.177703","volume":"7","author":"AB Nair","year":"2016","unstructured":"Nair, A. B. & Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 7, 27\u201331 (2016).","journal-title":"J. Basic Clin. Pharm."},{"key":"2299_CR108","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v067.i01","volume":"67","author":"D Bates","year":"2015","unstructured":"Bates, D., M\u00e4chler, M., Bolker, B. & Walker, S. Fitting linear mixed-effects models using lme4. J. Stat. Softw. 67, 1\u201348 (2015).","journal-title":"J. Stat. Softw."},{"key":"2299_CR109","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v082.i13","volume":"82","author":"A Kuznetsova","year":"2017","unstructured":"Kuznetsova, A., Brockhoff, P. B. & Christensen, R. H. B. lmerTest package: tests in linear mixed effects models. J. Stat. Softw. 82, 1\u201326 (2017).","journal-title":"J. Stat. Softw."},{"key":"2299_CR110","unstructured":"Andrews, S. C. FastQC: a quality control tool for high throughput sequence data. Version: 0.12.1 http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc (2010)."},{"key":"2299_CR111","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows\u2013Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"2299_CR112","doi-asserted-by":"publisher","first-page":"e112963","DOI":"10.1371\/journal.pone.0112963","volume":"9","author":"BJ Walker","year":"2014","unstructured":"Walker, B. J. et al. Pilon: an integrated tool for comprehensive microbial variant detection and genome assembly improvement. PLoS ONE 9, e112963 (2014).","journal-title":"PLoS ONE"},{"key":"2299_CR113","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/978-1-4939-0554-6_12","volume":"1151","author":"DE Deatherage","year":"2014","unstructured":"Deatherage, D. E. & Barrick, J. E. Identification of mutations in laboratory evolved microbes from next-generation sequencing data using breseq. Methods Mol. Biol. 1151, 165\u2013188 (2014).","journal-title":"Methods Mol. Biol."},{"key":"2299_CR114","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.molcel.2018.10.022","volume":"73","author":"Y Pu","year":"2019","unstructured":"Pu, Y. et al. ATP-dependent dynamic protein aggregation regulates bacterial dormancy depth critical for antibiotic tolerance. Mol. Cell 73, 143\u2013156.e4 (2019).","journal-title":"Mol. Cell"},{"key":"2299_CR115","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03251-21","volume":"13","author":"L Zuily","year":"2022","unstructured":"Zuily, L. et al. Copper induces protein aggregation, a toxic process compensated by molecular chaperones. mBio 13, e03251-21 (2022).","journal-title":"mBio"}],"container-title":["Nature Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41564-026-02299-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41564-026-02299-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41564-026-02299-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T11:36:47Z","timestamp":1778672207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41564-026-02299-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,6]]},"references-count":115,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["2299"],"URL":"https:\/\/doi.org\/10.1038\/s41564-026-02299-2","relation":{},"ISSN":["2058-5276"],"issn-type":[{"value":"2058-5276","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,6]]},"assertion":[{"value":"3 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A.L.G. serves on the scientific advisory boards of Seres Therapeutics, Taconic Biosciences and Piton Therapeutics. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}