title: Transport across the outer membrane porin of mycolic acid containing actinomycetales: Nocardia farcinica.
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.
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany. Electronic address: p.singh@jacobs-university.de.
authors.forename: Pratik Raj
authors.initials: PR
authors.lastname: Singh
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany.
authors.forename: Harsha
authors.initials: H
authors.lastname: Bajaj
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Benz
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Winterhalter
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany. Electronic address: mahendran.kozhinjampararadhakrishnan@chem.ox.ac.uk.
authors.forename: Kozhinjampara R
authors.initials: KR
authors.lastname: Mahendran
mesh_terms: D000583:Amikacin / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry; D000077727:Ertapenem; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D057927:Hydrophobic and Hydrophilic Interactions; D007612:Kanamycin / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009171:Mycolic Acids / Q000737:chemistry; D009615:Nocardia / Q000737:chemistry* / Q000378:metabolism; D018272:Porins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D040681:Structural Homology, Protein; D047090:beta-Lactams / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008081:Liposomes; D009171:Mycolic Acids; D018272:Porins; D011994:Recombinant Proteins; D047090:beta-Lactams; D007612:Kanamycin; D000583:Amikacin; D000077727:Ertapenem
keywords: Antibiotic resistance; Mycolata; Nocardia farcinica; Porin; Single channel electrophysiology