{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:11:00Z","timestamp":1791421860514,"version":"4.3.3"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Persister cells are a specific subset of bacteria capable of surviving exposure to lethal doses of antibiotics, leading to antibiotic therapy failures and infection relapses. This research explores the utilization of drug repositioning to target the Lon protease in <jats:italic>Salmonella<\/jats:italic> Typhimurium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>In this study, FDA-approved drugs sourced from the Drug Bank database were screened to identify existing pharmaceuticals with the potential to combat the Lon protease. The formation of persister cells in the presence of antibiotics, as well as the combination of antibiotics with potential Lon protease inhibitors, was examined. Furthermore, the expression of type II toxin-antitoxin system genes was analyzed to enhance our comprehension of the inhibitors\u2019 effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Molecular docking analysis revealed that Diosmin and Nafcillin exhibited strong binding affinity to the Lon protease. Molecular dynamics simulation trajectories analysis demonstrated that the interaction of these ligands with the enzyme did not induce instability; rather, the enzyme\u2019s structure remained stable. Combinations of ceftazidime and ciprofloxacin with either Nafcillin or Diosmin led to significant reductions in bacterial cell counts. Furthermore, the effectiveness of these combinations, when compared to antibiotics alone, highlighted the substantial impact of Nafcillin and Diosmin in reducing type II TA system gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest promising prospects for developing novel therapeutic approaches targeting persister cells to mitigate treatment failures in <jats:italic>Salmonella<\/jats:italic> infections.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1427312","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T05:18:30Z","timestamp":1725513510000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Targeting lon protease to inhibit persister cell formation in Salmonella Typhimurium: a drug repositioning approach"],"prefix":"10.3389","volume":"14","author":[{"given":"Negar","family":"Narimisa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabnam","family":"Razavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Khoshbayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Gharaghani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faramarz Masjedian","family":"Jazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.vacun.2023.03.002","article-title":"Effects of sub-inhibitory concentration of antibiotic and heat stress on the expression of type II TA system genes in Brucella spp","volume":"24","author":"Amraei","year":"2023","journal-title":"Vacunas."},{"key":"B2","doi-asserted-by":"publisher","first-page":"104194","DOI":"10.1016\/j.micpath.2020.104194","article-title":"The expression of type II TA system genes following exposure to the sub-inhibitory concentration of gentamicin and acid stress in Brucella spp","volume":"144","author":"Amraei","year":"2020","journal-title":"Microbial Pathogenesis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"456","DOI":"10.2174\/1389203715666140327114232","article-title":"A review of methods available to estimate solvent-accessible surface areas of soluble proteins in the folded and unfolded states","volume":"15","author":"Ausaf Ali","year":"2014","journal-title":"Curr. 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