Decreased expression of LamB and Odp1 complex is crucial for antibiotic resistance in Escherichia coli

J Proteomics. 2014 Feb 26:98:244-53. doi: 10.1016/j.jprot.2013.12.024. Epub 2014 Jan 9.

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.

Biological significance: 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.

Keywords: Antibiotic resistance; Escherichia coli; LamB; Odp1; Protein–protein interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Outer Membrane Proteins / biosynthesis*
  • Chlortetracycline / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Bacterial / drug effects*
  • Drug Resistance, Bacterial / genetics
  • Energy Metabolism / drug effects
  • Escherichia coli K12 / genetics
  • Escherichia coli K12 / metabolism*
  • Gene Expression Regulation, Bacterial / drug effects*
  • Gene Expression Regulation, Bacterial / genetics
  • Porins / biosynthesis*
  • Receptors, Virus / biosynthesis*

Substances

  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Porins
  • Receptors, Virus
  • maltoporins
  • Chlortetracycline