Transport across the outer membrane porin of mycolic acid containing actinomycetales: Nocardia farcinica

Biochim Biophys Acta. 2015 Feb;1848(2):654-61. doi: 10.1016/j.bbamem.2014.11.020. Epub 2014 Nov 23.

Abstract

The role of the outer-membrane channel from a mycolic acid containing Gram-positive bacteria Nocardia farcinica, which forms a hydrophilic pathway across the cell wall, was characterized. Single channel electrophysiology measurements and liposome swelling assays revealed the permeation of hydrophilic solutes including sugars, amino acids and antibiotics. The cation selective N. farcinica channel exhibited strong interaction with the positively charged antibiotics; amikacin and kanamycin, and surprisingly also with the negatively charged ertapenem. Voltage dependent kinetics of amikacin and kanamycin interactions were studied to distinguish binding from translocation. Moreover, the importance of charged residues inside the channel was investigated using mutational studies that revealed rate limiting interactions during the permeation.

Keywords: Antibiotic resistance; Mycolata; Nocardia farcinica; Porin; Single channel electrophysiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amikacin / chemistry
  • Anti-Bacterial Agents / chemistry*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biological Transport
  • Cell Membrane / chemistry*
  • Cell Membrane / metabolism
  • Cell Wall / chemistry
  • Ertapenem
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Hydrophobic and Hydrophilic Interactions
  • Kanamycin / chemistry
  • Liposomes / chemistry*
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Mutation
  • Mycolic Acids / chemistry
  • Nocardia / chemistry*
  • Nocardia / metabolism
  • Porins / chemistry*
  • Porins / genetics
  • Porins / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Static Electricity
  • Structural Homology, Protein
  • beta-Lactams / chemistry

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Liposomes
  • Mycolic Acids
  • Porins
  • Recombinant Proteins
  • beta-Lactams
  • Kanamycin
  • Amikacin
  • Ertapenem