{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T03:16:55Z","timestamp":1785554215107,"version":"3.56.0"},"reference-count":89,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T00:00:00Z","timestamp":1632614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM084176"],"award-info":[{"award-number":["R01GM084176"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Duke Pharmacological Sciences Training Program","award":["T32 GM007105"],"award-info":[{"award-number":["T32 GM007105"]}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF20CC0035580"],"award-info":[{"award-number":["NNF20CC0035580"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pyrithione (2-mercaptopyridine-N-oxide) is a metal binding modified pyridine, the antibacterial activity of which was described over 60 years ago. The formulation of zinc-pyrithione is commonly used in the topical treatment of certain dermatological conditions. However, the characterisation of the cellular uptake of pyrithione has not been elucidated, although an unsubstantiated assumption has persisted that pyrithione and\/or its metal complexes undergo a passive diffusion through cell membranes. Here, we have profiled specific membrane transporters from an unbiased interrogation of 532 E. coli strains of knockouts of genes encoding membrane proteins from the Keio collection. Two membrane transporters, FepC and MetQ, seemed involved in the uptake of pyrithione and its cognate metal complexes with copper, iron, and zinc. Additionally, the phenotypes displayed by CopA and ZntA knockouts suggested that these two metal effluxers drive the extrusion from the bacterial cell of potentially toxic levels of copper, and perhaps zinc, which hyperaccumulate as a function of pyrithione. The involvement of these distinct membrane transporters contributes to the understanding of the mechanisms of action of pyrithione specifically and highlights, more generally, the important role that membrane transporters play in facilitating the uptake of drugs, including metal\u2013drug compounds.<\/jats:p>","DOI":"10.3390\/molecules26195826","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T21:40:30Z","timestamp":1632778830000},"page":"5826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8756-0080","authenticated-orcid":false,"given":"Jesus Enrique","family":"Salcedo-Sora","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Crown St., Liverpool L69 7ZB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy T. R.","family":"Robison","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Duke University, 124 Science Drive, Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Zaengle-Barone","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Duke University, 124 Science Drive, Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9015-0998","authenticated-orcid":false,"given":"Katherine J.","family":"Franz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Duke University, 124 Science Drive, Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5838-7963","authenticated-orcid":false,"given":"Douglas B.","family":"Kell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Crown St., Liverpool L69 7ZB, UK"},{"name":"Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet, 2800 Kgs Lyngby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S0140-6736(15)00473-0","article-title":"Understanding the mechanisms and drivers of antimicrobial resistance","volume":"387","author":"Holmes","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/S1473-3099(16)30419-4","article-title":"UN commits to tackling antimicrobial resistance","volume":"16","author":"Mushtaq","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/S1473-3099(17)30633-3","article-title":"Addressing antimicrobial resistance in the UK and Europe","volume":"17","author":"Wells","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"eaau4679","DOI":"10.1126\/science.aau4679","article-title":"The challenge of antimicrobial resistance: What economics can contribute","volume":"364","author":"Roope","year":"2019","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1126\/science.aaa2868","article-title":"Infectious disease. A return to the pre-antimicrobial era?","volume":"347","author":"Baker","year":"2015","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-018-0141-x","article-title":"Drug combinations: A strategy to extend the life of antibiotics in the 21st century","volume":"17","author":"Tyers","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41586-019-1791-1","article-title":"A new antibiotic selectively kills Gram-negative pathogens","volume":"576","author":"Imai","year":"2019","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1126\/science.aar3777","article-title":"Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens","volume":"360","author":"Baker","year":"2018","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.4155\/fmc-2014-0032","article-title":"Ask the experts: How to curb antibiotic resistance and plug the antibiotics gap?","volume":"8","author":"Piddock","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Annunziato, G. (2019). Strategies to overcome antimicrobial resistance (AMR) making use of non-essential target inhibitors: A review. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235844"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Salcedo-Sora, J.E., and Kell, D.B. (2020). A quantitative survey of bacterial persistence in the presence of antibiotics: Towards antipersister antimicrobial discovery. Antibiotics, 9.","DOI":"10.3390\/antibiotics9080508"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mendes, P., Girardi, E., Superti-Furga, G., and Kell, D.B. (2020). Why most transporter mutations that cause antibiotic resistance are to efflux pumps rather than to import transporters. bioRxiv.","DOI":"10.1101\/2020.01.16.909507"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.tibtech.2015.02.001","article-title":"Membrane transporter engineering in industrial biotechnology and whole cell biocatalysis","volume":"33","author":"Kell","year":"2015","journal-title":"Trends Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kell, D.B. (2019). Control of Metabolite Efflux in Microbial Cell Factories. Current Advances and Future Prospects, CRC Press. [1st ed.].","DOI":"10.31219\/osf.io\/xg9jh"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1128\/CMR.19.2.382-402.2006","article-title":"Clinically Relevant Chromosomally Encoded Multidrug Resistance Efflux Pumps in Bacteria","volume":"19","author":"Piddock","year":"2006","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1093\/jac\/dkz370","article-title":"The 2019 Garrod lecture: MDR efflux in gram-negative bacteria\u2014How understanding resistance led to a new tool for drug discovery","volume":"74","author":"Piddock","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16","DOI":"10.2174\/1389450119666180426103300","article-title":"Bacterial multidrug efflux proteins: A major mechanism of antimicrobial resistance","volume":"20","author":"Ahmad","year":"2018","journal-title":"Curr. Drug Targets"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s12551-018-0404-9","article-title":"Antimicrobial resistance (AMR) nanomachines\u2014Mechanisms for fluoroquinolone and glycopeptide recognition, efflux and\/or deactivation","volume":"10","author":"Harding","year":"2018","journal-title":"Biophys. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1080\/07853890701195262","article-title":"Efflux pumps as antimicrobial resistance mechanisms","volume":"39","author":"Poole","year":"2007","journal-title":"Ann. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s00249-017-1238-2","article-title":"Efflux drug transporters at the forefront of antimicrobial resistance","volume":"46","author":"Rahman","year":"2017","journal-title":"Eur. Biophys. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/14728222.2017.1265105","article-title":"Efflux as a mechanism of antimicrobial drug resistance in clinical relevant microorganisms: The role of efflux inhibitors","volume":"21","author":"Willers","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vrancianu, C.O., Gheorghe, I., Dobre, E.-G., Barbu, I.C., Cristian, R.E., Popa, M., Lee, S.H., Limban, C., Vlad, I.M., and Chifiriuc, M.C. (2020). Emerging strategies to combat \u03b2-lactamase producing ESKAPE pathogens. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228527"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41598-020-79791-0","article-title":"Comprehensive study of antimicrobial susceptibility pattern and extended spectrum beta-lactamase (ESBL) prevalence in bacteria isolated from urine samples","volume":"11","author":"Gharavi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Eiamphungporn, W., Schaduangrat, N., Malik, A.A., and Nantasenamat, C. (2018). Tackling the antibiotic resistance caused by class A \u03b2-lactamases through the use of \u03b2-lactamase inhibitory protein. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082222"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1089\/fpd.2016.2191","article-title":"Occurrence of extended-spectrum \u03b2-lactamases, plasmid-mediated quinolone resistance, and disinfectant resistance genes in Escherichia coli isolated from ready-to-eat meat products","volume":"14","author":"Li","year":"2017","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.tim.2016.06.009","article-title":"Antibiotic adjuvants: Rescuing antibiotics from resistance","volume":"24","author":"Wright","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrmicro3028","article-title":"Antimicrobial activity of metals: Mechanisms, molecular targets and applications","volume":"11","author":"Lemire","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1111\/jam.13681","article-title":"Contact killing and antimicrobial properties of copper","volume":"124","author":"Vincent","year":"2018","journal-title":"J. Appl. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Arendsen, L.P., Thakar, R., and Sultan, A.H. (2019). The use of copper as an antimicrobial agent in health care, including obstetrics and gynecology. Clin. Microbiol. Rev., 32.","DOI":"10.1128\/CMR.00125-18"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1021\/acs.chemrev.0c00921","article-title":"Antimicrobial peptides and copper(II) ions: Novel therapeutic opportunities","volume":"121","author":"Portelinha","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1093\/jac\/dkm201","article-title":"Three novel highly charged copper-based biocides: Safety and efficacy against healthcare-associated organisms","volume":"60","author":"Gant","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1128\/AEM.02766-10","article-title":"Metallic copper as an antimicrobial surface","volume":"77","author":"Grass","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1021\/acschembio.0c00900","article-title":"Protein folding stability changes across the proteome reveal targets of cu toxicity in E. coli","volume":"16","author":"Wiebelhaus","year":"2021","journal-title":"ACS Chem. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1021\/acsinfecdis.8b00037","article-title":"Copper influences the antibacterial outcomes of a \u03b2-lactamase-activated prochelator against drug-resistant bacteria","volume":"4","author":"Jackson","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1021\/acsinfecdis.9b00112","article-title":"Dual-pharmacophore pyrithione-containing cephalosporins kill both replicating and nonreplicating mycobacterium tuberculosis","volume":"5","author":"Quezada","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1039\/C6MT00172F","article-title":"Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans","volume":"9","author":"Helsel","year":"2017","journal-title":"Metallomics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"213474","DOI":"10.1016\/j.ccr.2020.213474","article-title":"Biomedical applications of copper ionophores","volume":"422","author":"Oliveri","year":"2020","journal-title":"Coord. Chem. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Djoko, K.Y., Achard, M.E.S., Phan, M.-D., Lo, A.W., Miraula, M., Prombhul, S., Hancock, S.J., Peters, K.M., Sidjabat, H.E., and Harris, P.N. (2018). Copper ions and coordination complexes as novel carbapenem adjuvants. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.02280-17"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1128\/AAC.14.1.60","article-title":"Mechanism of the antimicrobial action of pyrithione: Effects on membrane transport, ATP levels, and protein synthesis","volume":"14","author":"Chandler","year":"1978","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5753","DOI":"10.1128\/AAC.00724-11","article-title":"Zinc pyrithione inhibits yeast growth through copper influx and inactivation of iron-sulfur proteins","volume":"55","author":"Reeder","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","first-page":"500","article-title":"The influence of chemical constitution on antibacterial activity. VIII. 2-mercaptopyridine-n-oxide, and some general observations on metalbinding agents","volume":"37","author":"Albert","year":"1956","journal-title":"Br. J. Exp. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lanthaler, K., Bilsland, E., Dobson, P., Moss, H.J., Pir, P., Kell, D.B., and Oliver, S.G. (2011). Genome-wide assessment of the carriers in-volved in the cellular uptake of drugs: A model system in yeast. BMC Biol., 9.","DOI":"10.1186\/1741-7007-9-70"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/nchembio.1590","article-title":"The solute carrier SLC35F2 enables YM155-mediated DNA damage toxicity","volume":"10","author":"Winter","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nrd3028","article-title":"Membrane transporters in drug development","volume":"9","author":"Giacomini","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/cpt.1224","article-title":"The international transporter consortium: Summarizing advances in the role of transporters in drug development","volume":"104","author":"Giacomini","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nrd2438","article-title":"Carrier-mediated cellular uptake of pharmaceutical drugs: An exception or the rule?","volume":"7","author":"Dobson","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"163","DOI":"10.2174\/156802609787521616","article-title":"Implications of the dominant role of cellular transporters in drug uptake","volume":"9","author":"Dobson","year":"2009","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.drudis.2012.11.008","article-title":"The promiscuous binding of pharmaceutical drugs and their transporter-mediated uptake into cells: What we (need to) know and how we can do so","volume":"18","author":"Kell","year":"2013","journal-title":"Drug Discov. Today"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3389\/fphar.2014.00231","article-title":"How drugs get into cells: Tested and testable predictions to help discriminate between transporter-mediated uptake and lipoidal bilayer diffusion","volume":"5","author":"Kell","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/s41589-020-0483-3","article-title":"A widespread role for SLC transmembrane transporters in resistance to cytotoxic drugs","volume":"16","author":"Girardi","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/msb4100050","article-title":"Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: The Keio collection","volume":"2","author":"Baba","year":"2006","journal-title":"Mol. Syst. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/msb.2009.92","article-title":"Update on the Keio collection of Escherichia coli single-gene deletion mutants","volume":"5","author":"Yamamoto","year":"2009","journal-title":"Mol. Syst. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/dnares\/dsi012","article-title":"Complete set of ORF clones of Escherichia coli ASKA library (A complete set of E. coli K-12 ORF archive): Unique resources for biological research","volume":"12","author":"Kitagawa","year":"2005","journal-title":"DNA Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/978-1-4939-2398-4_4","article-title":"Identification of essential genes and synthetic lethal gene combinations in Escherichia coli K-12","volume":"1279","author":"Mori","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1128\/mr.60.4.641-696.1996","article-title":"Flow cytometry and cell sorting of heterogeneous microbial populations: The importance of single-cell analysis","volume":"60","author":"Davey","year":"1996","journal-title":"Microbiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1099\/mic.0.000777","article-title":"Very rapid flow cytometric assessment of antimicrobial susceptibility during the apparent lag phase of microbial (re)growth","volume":"165","author":"Jindal","year":"2019","journal-title":"Microbiology"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Jindal, S., Yang, L., Day, P.J., and Kell, D.B. (2019). Involvement of multiple influx and efflux transporters in the accumulation of cationic fluorescent dyes by Escherichia coli. BMC Microbiol., 19.","DOI":"10.1186\/s12866-019-1561-0"},{"key":"ref_58","first-page":"001016","article-title":"A palette of fluorophores that are differentially accumulated by wild-type and mutant strains of Escherichia coli: Surrogate ligands for profiling bacterial membrane transporters","volume":"167","author":"Jindal","year":"2021","journal-title":"Microbiology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1365-2672.1988.tb03384.x","article-title":"The influence of pyrithione on the growth of micro-organisms","volume":"64","author":"Khattar","year":"1988","journal-title":"J. Appl. Bacteriol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3385","DOI":"10.1128\/aem.61.9.3385-3390.1995","article-title":"Mechanism of pyrithione-induced membrane depolarization in Neurospora crassa","volume":"61","author":"Ermolayeva","year":"1995","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1039\/C8MT00239H","article-title":"Copper stress in Staphylococcus aureus leads to adaptive changes in central carbon metabolism","volume":"11","author":"Tarrant","year":"2019","journal-title":"Metallomics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1365-2133.2011.10571.x","article-title":"The antifungal mechanism of action of zinc pyrithione","volume":"165","author":"Reeder","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4266","DOI":"10.1021\/jacs.6b12921","article-title":"Copper ATPase CopA from Escherichia coli: Quantitative correlation between ATPase activity and vectorial copper transport","volume":"139","author":"Wijekoon","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/mmi.14522","article-title":"Copper tolerance in bacteria requires the activation of multiple accessory pathways","volume":"114","author":"Giachino","year":"2020","journal-title":"Mol. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/B978-0-12-394390-3.00005-7","article-title":"Toward a molecular understanding of metal transport by P1B-Type ATPases","volume":"69","author":"Rosenzweig","year":"2012","journal-title":"Curr. Top Membr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"28455","DOI":"10.1074\/jbc.M301415200","article-title":"The metal specificity and selectivity of ZntA from Escherichia coli using the acylphosphate intermediate","volume":"278","author":"Hou","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1073\/pnas.97.2.652","article-title":"CopA: An Escherichia coli Cu(I)-translocating P-type ATPase","volume":"97","author":"Rensing","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"46987","DOI":"10.1074\/jbc.M208490200","article-title":"Biochemical characterization of CopA, the Escherichia coli Cu(I)-translocating P-type ATPase","volume":"277","author":"Fan","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1021\/bi027096p","article-title":"Understanding copper trafficking in bacteria: Interaction between the copper transport protein CopZ and the N-terminal domain of the copper ATPase CopA from Bacillus subtilis","volume":"42","author":"Banci","year":"2003","journal-title":"Biochemistry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"20492","DOI":"10.1074\/jbc.M114.577668","article-title":"Mechanism of ATPase-mediated Cu+ export and delivery to periplasmic chaperones: The interaction of Escherichia coli CopA and CusF","volume":"289","author":"Thompson","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0378-1097(03)00095-8","article-title":"CopZ from Bacillus subtilisinteracts in vivo with a copper exporting CPx-type ATPase CopA","volume":"220","author":"Radford","year":"2003","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.bioelechem.2006.03.016","article-title":"Redox sensing by Escherichia coli: Effects of copper ions as oxidizers on proton-coupled membrane transport","volume":"70","author":"Kirakosyan","year":"2007","journal-title":"Bioelectrochemistry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tibtech.2006.06.008","article-title":"Rationalizing membrane protein overexpression","volume":"24","author":"Wagner","year":"2006","journal-title":"Trends Biotechnol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1017\/S0033583500003504","article-title":"Overexpression of integral membrane proteins for structural studies","volume":"28","author":"Grisshammer","year":"1995","journal-title":"Q. Rev. Biophys."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1111\/j.1365-2958.1997.mmi518.x","article-title":"Zinc(II) tolerance in Escherichia coli K-12: Evidence that the ZntA gene (o732) encodes a cation transport ATPase","volume":"25","author":"Beard","year":"1997","journal-title":"Mol. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1080\/15216540050033168","article-title":"Expression of ZntA, a zinc-transporting P 1-type ATPase, is specifically regulated by zinc and cadmium","volume":"49","author":"Noll","year":"2000","journal-title":"IUBMB Life"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0014-5793(00)01509-X","article-title":"Cd(II), Pb(II) and Zn(II) ions regulate expression of the metal-transporting P-type ATPase ZntA in Escherichia coli","volume":"473","author":"Binet","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"14268","DOI":"10.1021\/bi050761k","article-title":"Kinetic analysis of metal binding to the amino-terminal domain of ZntA by monitoring metal\u2212thiolate charge-transfer complexes","volume":"44","author":"Dutta","year":"2005","journal-title":"Biochemistry"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.1074\/jbc.275.6.3873","article-title":"The ATP hydrolytic activity of purified ZntA, a Pb(II)\/Cd(II)\/Zn(II)-translocating ATPase from Escherichia coli","volume":"275","author":"Sharma","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"E10596","DOI":"10.1073\/pnas.1811003115","article-title":"Noncanonical role for the binding protein in substrate uptake by the MetNI methionine ATP Binding Cassette (ABC) transporter","volume":"115","author":"Nguyen","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5513","DOI":"10.1128\/JB.184.19.5513-5517.2002","article-title":"The Escherichia coli metD Locus encodes an ABC transporter which includes Abc (MetN), YaeE (MetI), and YaeC (MetQ)","volume":"184","author":"Merlin","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e46615","DOI":"10.7554\/eLife.46615","article-title":"Profiling the Escherichia coli membrane protein interactome captured in peptidisc libraries","volume":"8","author":"Carlson","year":"2019","journal-title":"Elife"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1128\/jb.166.3.930-936.1986","article-title":"Escherichia coli K-12 envelope proteins specifically required for ferrienterobactin uptake","volume":"166","author":"Pierce","year":"1986","journal-title":"J. Bacteriol."},{"key":"ref_84","unstructured":"R Core Team (2020). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Ritz, C., Baty, F., Streibig, J.C., and Gerhard, D. (2015). Dose-response analysis using R. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0146021"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/pst.426","article-title":"Guidelines for accurate EC50\/IC50 estimation","volume":"10","author":"Sebaugh","year":"2011","journal-title":"Pharm. Stat."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/molbev\/mst187","article-title":"Growth rates made easy","volume":"31","author":"Hall","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Vaas, L.A.I., Sikorski, J., Michael, V., G\u00f6ker, M., and Klenk, H.-P. (2012). Visualization and curve-parameter estimation strategies for efficient exploration of phenotype microarray kinetics. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034846"},{"key":"ref_89","unstructured":"Petzoldt, T. (2021, June 16). Growthrates: Estimate Growth Rates from Experimental Data. Available online: https:\/\/github.com\/tpetzoldt\/growthrates."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/19\/5826\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:05:11Z","timestamp":1760166311000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/19\/5826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,26]]},"references-count":89,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["molecules26195826"],"URL":"https:\/\/doi.org\/10.3390\/molecules26195826","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,26]]}}}