{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:33:53Z","timestamp":1792193633957,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K18485"],"award-info":[{"award-number":["20K18485"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Magnesium hydroxide nanoparticles are widely used in medicinal and hygiene products because of their low toxicity, environment-friendliness, and low cost. Here, we studied the effects of three different sizes of magnesium hydroxide nanoparticles on antibacterial activity: NM80, NM300, and NM700. NM80 (D50 = 75.2 nm) showed a higher bactericidal effect against Escherichia coli than larger nanoparticles (D50 = 328 nm (NM300) or 726 nm (NM700)). Moreover, NM80 showed a high bactericidal effect against not only exponential cells but also persister cells, which are difficult to eliminate owing to their high tolerance to antibiotics. NM80 eliminated strains in which magnesium-transport genes were knocked out and exhibited a bactericidal effect similar to that observed in the wild-type strain. The bactericidal action involved physical cell damage, as confirmed using scanning electron microscopy, which showed that E. coli cells treated with NM80 were directly injured.<\/jats:p>","DOI":"10.3390\/nano11061584","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T21:58:32Z","timestamp":1623880712000},"page":"1584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Magnesium Hydroxide Nanoparticles Kill Exponentially Growing and Persister Escherichia coli Cells by Causing Physical Damage"],"prefix":"10.3390","volume":"11","author":[{"given":"Yohei","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Health Promotion, Division of Infections and Molecular Biology, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaede","family":"Okita","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Division of Infections and Molecular Biology, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kudo","sequence":"additional","affiliation":[{"name":"Kyowa Chemical Industry Co., Ltd., Hayashida-cho, Sakaide 762-0012, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao Nguyen Duy","family":"Phuong","sequence":"additional","affiliation":[{"name":"Kyowa Chemical Industry Co., Ltd., Hayashida-cho, Sakaide 762-0012, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihito","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Kyowa Chemical Industry Co., Ltd., Hayashida-cho, Sakaide 762-0012, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshie","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Division of Infections and Molecular Biology, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-5683","authenticated-orcid":false,"given":"Wataru","family":"Ariyoshi","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Division of Infections and Molecular Biology, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1152-3248","authenticated-orcid":false,"given":"Ryota","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Division of Infections and Molecular Biology, Kyushu Dental University, Kitakyushu 803-8580, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1097\/00045391-199508000-00006","article-title":"Effects of Aluminum\/Magnesium Hydroxide and Calcium Carbonate on Esophageal and Gastric pH in Subjects with Heartburn","volume":"2","author":"Decktor","year":"1995","journal-title":"Am. J. Ther."},{"key":"ref_2","first-page":"321","article-title":"Constipation in elderly long-stay patients: Its treatment by magnesium hydroxide and bulk-laxative","volume":"19","author":"Kinnunen","year":"1987","journal-title":"Ann. Clin. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1016\/j.arabjc.2018.10.001","article-title":"Promotion of seed germination and seedling growth of Zea mays by magnesium hydroxide nanoparticles synthesized by the filtrate from Aspergillus niger","volume":"13","author":"Shinde","year":"2020","journal-title":"Arab. J. Chem"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.apsusc.2017.07.101","article-title":"Hydrothermal synthesis of 4ZnO\u00b7B2O3\u00b7H2O\/RGO hybrid material and its flame retardant behavior in flexible PVC and magnesium hydroxide composites","volume":"425","author":"Zhang","year":"2017","journal-title":"Appl. Surf. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.polymdegradstab.2016.06.011","article-title":"Synergistic effect of an aromatic boronic acid derivative and magnesium hydroxide on the flame retardancy of epoxy resin","volume":"130","author":"Zhang","year":"2016","journal-title":"Polym. Degrad. Stab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.exer.2017.10.002","article-title":"Co-instillation of nano-solid magnesium hydroxide enhances corneal permeability of dissolved timolol","volume":"165","author":"Nagai","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6917","DOI":"10.1021\/acsnano.8b02365","article-title":"Modified Magnesium Hydroxide Nanoparticles Inhibit the Inflammatory Response to Biodegradable Poly(lactide-co-glycolide) Implants","volume":"12","author":"Lih","year":"2018","journal-title":"ACS Nano"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Halbus, A.F., Horozov, T.S., and Paunov, V.N. (2019). Controlling the Antimicrobial Action of Surface Modified Magnesium Hydroxide Nanoparticles. Biomimetics, 4.","DOI":"10.3390\/biomimetics4020041"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1021\/am302910q","article-title":"Investigation of antibacterial activity and related mechanism of a series of nano-Mg(OH)2","volume":"5","author":"Pan","year":"2013","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1002\/fsn3.1646","article-title":"Structural characterization and catalytic sterilization performance of a TiO2 nano-photocatalyst","volume":"8","author":"Yang","year":"2020","journal-title":"Food Sci. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.jphotobiol.2018.02.003","article-title":"Blue light irradiation triggers the antimicrobial potential of ZnO nanoparticles on drug-resistant Acinetobacter baumannii","volume":"180","author":"Yang","year":"2018","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41598-021-81305-5","article-title":"The interaction of Ag2O nanoparticles with Escherichia coli: Inhibition-sterilization process","volume":"11","author":"Li","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s12275-019-8629-2","article-title":"Ribosome dependence of persister cell formation and resuscitation","volume":"57","author":"Wood","year":"2019","journal-title":"J. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3181\/00379727-50-13773","article-title":"Observations on the Mechanism of Action of Penicillin","volume":"50","author":"Hobby","year":"1942","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1126\/science.1099390","article-title":"Bacterial persistence as a phenotypic switch","volume":"305","author":"Balaban","year":"2004","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"D\u00f6rr, T., Vuli\u0107, M., and Lewis, K. (2010). Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000317"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1111\/1462-2920.14093","article-title":"Single cell observations show persister cells wake based on ribosome content","volume":"20","author":"Kim","year":"2018","journal-title":"Environ. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"126709","DOI":"10.1016\/j.micres.2021.126709","article-title":"DNA adenine methylation is involved in persister formation in E. coli","volume":"246","author":"Xu","year":"2021","journal-title":"Microbiol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1111\/jam.14434","article-title":"Interkingdom signal indole inhibits Pseudomonas aeruginosa persister cell waking","volume":"127","author":"Zhang","year":"2019","journal-title":"J. Appl. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41586-019-1521-8","article-title":"Salmonella persisters promote the spread of antibiotic resistance plasmids in the gut","volume":"573","author":"Bakkeren","year":"2019","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-04472-6","article-title":"Activity of acetyltransferase toxins involved in Salmonella persister formation during macrophage infection","volume":"9","author":"Rycroft","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1111\/1462-2920.14075","article-title":"Viable but non-culturable and persistence describe the same bacterial stress state","volume":"20","author":"Kim","year":"2018","journal-title":"Environ. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1128\/AAC.02135-12","article-title":"Arrested protein synthesis increases persister-like cell formation","volume":"57","author":"Kwan","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"413","DOI":"10.3389\/fmicb.2018.00413","article-title":"Identification of Genes Involved in Bacteriostatic Antibiotic-Induced Persister Formation","volume":"9","author":"Cui","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.3389\/fmicb.2017.01917","article-title":"Generation of persister cells of Pseudomonas aeruginosa and Staphylococcus aureus by chemical treatment and evaluation of their susceptibility to membrane-targeting agents","volume":"8","author":"Grassi","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.3389\/fmicb.2018.01724","article-title":"Novel glycopolymer eradicates antibiotic-and CCCP-induced persister cells in Pseudomonas aeruginosa","volume":"9","author":"Narayanaswamy","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.molcel.2018.10.022","article-title":"ATP-dependent dynamic protein aggregation regulates bacterial dormancy depth critical for antibiotic tolerance","volume":"73","author":"Pu","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.ijantimicag.2018.09.006","article-title":"Bacteriophage Sb-1 enhances antibiotic activity against biofilm, degrades exopolysaccharide matrix and targets persisters of Staphylococcus aureus","volume":"52","author":"Tkhilaishvili","year":"2018","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100792","DOI":"10.1016\/j.isci.2019.100792","article-title":"Persister Cells Resuscitate Using Membrane Sensors that Activate Chemotaxis, Lower cAMP Levels, and Revive Ribosomes","volume":"23","author":"Yamasaki","year":"2020","journal-title":"iScience"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"622798","DOI":"10.3389\/fmicb.2021.622798","article-title":"Thymine Sensitizes Gram-Negative Pathogens to Antibiotic Killing","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1111\/1462-2920.12873","article-title":"Combatting bacterial infections by killing persister cells with mitomycin C","volume":"17","author":"Kwan","year":"2015","journal-title":"Environ. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Moreira Martins, P.M., Gong, T., de Souza, A.A., and Wood, T.K. (2020). Copper Kills Escherichia coli Persister Cells. Antibiotics, 9.","DOI":"10.3390\/antibiotics9080506"},{"key":"ref_33","first-page":"98","article-title":"Nachr Ges wiss goettingen","volume":"2","author":"Scherrer","year":"1918","journal-title":"Math. Phys."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Baba, T., Ara, T., Hasegawa, M., Takai, Y., Okumura, Y., Baba, M., Datsenko, K.A., Tomita, M., Wanner, B.L., and Mori, H. (2006). Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: The Keio collection. Mol. Syst. Biol., 2.","DOI":"10.1038\/msb4100050"},{"key":"ref_35","unstructured":"Sambrook, J., Fritsch, E.F., and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1084\/jem.99.2.167","article-title":"Plaque formation and isolation of pure lines with poliomyelitis viruses","volume":"99","author":"Dulbecco","year":"1954","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"496","DOI":"10.3389\/fcimb.2020.00496","article-title":"Reactive Oxygen Species Penetrate Persister Cell Membranes of Escherichia coli for Effective Cell Killing","volume":"10","author":"Kawano","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1128\/jb.126.3.1096-1103.1976","article-title":"Mutants in three genes affecting transport of magnesium in Escherichia coli: Genetics and physiology","volume":"126","author":"Park","year":"1976","journal-title":"J. Bacteriol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5689","DOI":"10.1073\/pnas.1703415114","article-title":"Increasing intracellular magnesium levels with the 31-amino acid MgtS protein","volume":"114","author":"Wang","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1111\/j.1365-2958.1991.tb01984.x","article-title":"Magnesium transport in Salmonella typhimurium: The influence of new mutations conferring Co2+ resistance on the CorA Mg2+ transport system","volume":"5","author":"Gibson","year":"1991","journal-title":"Mol. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1021\/bi00173a020","article-title":"Translocation of metal phosphate via the phosphate inorganic transport system of Escherichia coli","volume":"33","author":"Abee","year":"1994","journal-title":"Biochemistry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jsb.2003.10.010","article-title":"Evolutionary history and higher order classification of AAA+ ATPases","volume":"146","author":"Iyer","year":"2004","journal-title":"J. Struct. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Nepal, S., and Kumar, P. (2020). Growth, Cell Division, and Gene Expression of Escherichia coli at Elevated Concentrations of Magnesium Sulfate: Implications for Habitability of Europa and Mars. Microorganisms, 8.","DOI":"10.3390\/microorganisms8050637"},{"key":"ref_44","unstructured":"Council, N.R. (2000). Toxicological risks of selected flame-retardant chemicals. National Research Council (US) Subcommittee on Flame-Retardant Chemicals, National Academy Press."}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/11\/6\/1584\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:17:06Z","timestamp":1760163426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/11\/6\/1584"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,16]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["nano11061584"],"URL":"https:\/\/doi.org\/10.3390\/nano11061584","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,16]]}}}