title: Decreased expression of LamB and Odp1 complex is crucial for antibiotic resistance in Escherichia coli.
abstract: We previously revealed a negative regulation of LamB in chlortetracycline-resistant Escherichia coli strain. In the present study, we first showed that the negative regulation, which was characterized by decreased abundance of LamB with elevated growth of its gene-deleted mutant in medium with antibiotics, was a general response in resistance to different classes of antibiotics using 2-DE based proteomics or/and genetically gene-deletion mutant of LamB. Then, we revealed the interaction of LamB and Odp1 which catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2, and found the decrease of the complex in antibiotic-resistant strains with a minimum inhibitory concentration dose-dependent manner. Further spectrofluorometry assay indicated that LamB served as a porin to influx an antibiotic. Finally, we showed that the decreased expression of LamB and Odp1 was detected in almost of all 34 multidrug-resistant strains, which suggested that LamB and Odp1 were biomarkers for identification of antibiotic-resistant E. coli. Our results indicated that the interaction of an outer membrane protein with an energy metabolic enzyme constructed an efficient pathway to resist antibiotics. These findings provide novel insights into the mechanisms of antibiotic resistance.
  
  
  CONCLUSIONS
  Our data indicate that the negative regulation by LamB is widely detected in antibiotic-resistant E. coli. LamB serves as a porin to influx an antibiotic and is interacted with Odp1. The complex decreases in antibiotic-resistant strains with a MIC dose-dependent manner. Our findings indicate that interaction of outer membrane protein with energy metabolic enzyme constructs an efficient pathway to resist antibiotics and provides novel insights into the mechanisms of antibiotic resistance.
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, PR China; Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring (School of Life Sciences, Fujian Agriculture and Forestry University), Fuzhou 35002, PR China.
authors.forename: Xiang-min
authors.initials: XM
authors.lastname: Lin
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, PR China.
authors.forename: Man-jun
authors.initials: MJ
authors.lastname: Yang
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Center for Proteomics and Metabolomics, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, University City, Guangzhou 510006, PR China. Electronic address: pxuanx@sysu.edu.cn.
authors.forename: Xuan-Xian
authors.initials: XX
authors.lastname: Peng
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis*; D002751:Chlortetracycline / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects; D048168:Escherichia coli K12 / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects* / Q000235:genetics; D018272:Porins / Q000096:biosynthesis*; D011991:Receptors, Virus / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D018272:Porins; D011991:Receptors, Virus; C016532:maltoporins; D002751:Chlortetracycline
keywords: Antibiotic resistance; Escherichia coli; LamB; Odp1; Protein–protein interaction