{ "labelLang" : "hun", "responseDate" : "2024-03-28 12:39", "content" : { "otype" : "JournalArticle", "mtid" : 30773626, "status" : "VALIDATED", "published" : true, "comment" : "College of Marine Life Sciences, MOE Key Laboratory of Marine Genetics and Breeding, Ocean University of China, Qingdao, China \n Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China \n Department of Chemistry, University of Nebraska—LincolnNE, United States \n Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, China \n Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China \n Export Date: 27 August 2019 \n Correspondence Address: Wang, Y.; College of Marine Life Sciences, MOE Key Laboratory of Marine Genetics and Breeding, Ocean University of ChinaChina; email: wangy12@ouc.edu.cn \n Chemicals/CAS: ampicillin, 69-52-3, 69-53-4, 7177-48-2, 74083-13-9, 94586-58-0; cyanocobalamin, 53570-76-6, 68-19-9, 8064-09-3; indole, 120-72-9; kanamycin, 11025-66-4, 61230-38-4, 8063-07-8 \n Funding details: Qingdao \n Funding details: China Academy of Space Technology, YESS20160009 \n Funding details: National Natural Science Foundation of China, 31770925, 41506160, 31722003, 31370847, 31870023, 31571970 \n Funding text 1: We are grateful to Yaoyao Li of Shandong University and Guoliang Qian of Nanjing Agriculture University for supplying bacterial strains. This work was supported by the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology (Qingdao) (grant \n Funding text 2: 2018SDKJ0406-4), the National Natural Science Foundation of China (grants 31870023, 31722003, 31571970, 31770925, 41506160, and 31370847), and the Young Elite Scientists Sponsorship Program by CAST (grant YESS20160009).\nCollege of Marine Life Sciences, MOE Key Laboratory of Marine Genetics and Breeding, Ocean University of China, Qingdao, China \n Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China \n Department of Chemistry, University of Nebraska—LincolnNE, United States \n Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, China \n Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China \n Cited By :5 \n Export Date: 24 August 2020 \n Correspondence 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Several studies indicate that indole, an interkingdom signaling molecule, increases bacterial antibiotic resistance. However, the mechanism through which indole reduces antibiotic resistance is largely unknown. In this study, we demonstrated a novel mechanism for indole-mediated reversal of intrinsic antibiotic resistance in Lysobacter. This reversal was facilitated by a novel BtuD-associated dual-function importer that can transfer both vitamin B12 and antibiotics. Indole stimulated btuD overexpression and promoted efficient absorption of extracellular vitamin B12; meanwhile, the weak selectivity of the importer caused cells to take up excessive doses of antibiotics that resulted in cell death. Consistently, btuD deletion and G48Y/K49D substitution led to marked reductions in the uptake of both antibiotics and vitamin B12. This novel mechanism is common across multiple bacterial species, among which the Q-loop amino acid of BtuD proteins is Glu (E) instead of Gln (Q). Interestingly, the antibiotic resistance of Lysobacter spp. can be restored by another small quorum sensing signaling factor, 13-methyltetradecanoic acid, designated LeDSF, in response to bacterial population density. This work highlights the mechanisms underlying dynamic regulation of bacterial antibiotic resistance by small signaling molecules and suggests that the effectiveness of traditional antibiotics could be increased by coupling them with appropriate signaling molecules. IMPORTANCE Recently, signaling molecules were found to play a role in mediating antibiotic resistance. In this study, we demonstrated that indole reversed the intrinsic antibiotic resistance (IRAR) of multiple bacterial species by promoting the expression of a novel dual-function importer. In addition, population-dependent behavior induced by 13-methyltetradecanoic acid, a quorum sensing signal molecule designated LeDSF, was involved in the IRAR process. 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