title: Intermediate-type vancomycin resistance (VISA) in genetically-distinct Staphylococcus aureus isolates is linked to specific, reversible metabolic alterations.
abstract: Intermediate (VISA-type) vancomycin resistance in Staphylococcus aureus has been associated with a range of physiologic and genetic alterations. Previous work described the emergence of VISA-type resistance in two clonally-distinct series of isolates. In both series (the first belonging to MRSA clone ST8-USA300, and the second to ST5-USA100), resistance was conferred by a single mutation in yvqF (a negative regulator of the vraSR two-component system associated with vancomycin resistance). In the USA300 series, resistance was reversed by a secondary mutation in vraSR. In this study, we combined systems-level metabolomic profiling with statistical modeling techniques to discover specific, reversible metabolic alterations associated with the VISA phenotype.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Alexander
authors.affiliation: Laboratory of Microbiology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Susana
authors.initials: S
authors.lastname: Gardete
authors.affiliation: Department of Statistics, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Haim Y
authors.initials: HY
authors.lastname: Bar
authors.affiliation: Department of Biological Statistics and Computational Biology and Department of Statistical Sciences, Cornell University, Ithaca, New York, United States of America.
authors.forename: Martin T
authors.initials: MT
authors.lastname: Wells
authors.affiliation: Laboratory of Microbiology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tomasz
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College, New York, New York, United States of America; Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Kyu Y
authors.initials: KY
authors.lastname: Rhee
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002853:Chromatography, Liquid; D004268:DNA-Binding Proteins / Q000378:metabolism; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D015233:Models, Statistical; D025341:Principal Component Analysis; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism*; D020713:Vancomycin Resistance / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C478170:VraR protein, Staphylococcus aureus; C478169:VraS protein, Staphylococcus aureus