title: Activated ADI pathway: the initiator of intermediate vancomycin resistance in Staphylococcus aureus.
abstract: Comparative proteomic profiling between 2 vancomycin-intermediate Staphylococcus aureus (VISA) strains, Mu50Ω-vraSm and Mu50Ω-vraSm-graRm, and vancomycin-susceptible S. aureus (VSSA) strain Mu50Ω revealed upregulated levels of catabolic ornithine carbamoyltransferase (ArcB) of the arginine catabolism pathway in VISA strains. Subsequent analyses showed that the VISA strains have higher levels of cellular ATP and ammonia, which are by-products of arginine catabolism, and displayed thicker cell walls. We postulate that elevated cytoplasmic ammonia and ATP molecules, resulting from activated arginine catabolism upon acquisition of vraS and graR mutations, are important requirements facilitating cell wall biosynthesis, thereby contributing to thickened cell wall and consequently reduced vancomycin susceptibility in VISA strains.
authors.affiliation: a UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Malaysia.
authors.forename: Xin-Ee
authors.initials: XE
authors.lastname: Tan
authors.affiliation: a UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Malaysia.|b Department of Bacteriology, School of Medicine, Juntendo University, Japan.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Neoh
authors.affiliation: a UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Malaysia.|c Taylor's University Lakeside Campus, School of Biosciences, Malaysia.
authors.forename: Mee-Lee
authors.initials: ML
authors.lastname: Looi
authors.affiliation: a UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Malaysia.
authors.forename: Siok Fong
authors.initials: SF
authors.lastname: Chin
authors.affiliation: d Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Japan.
authors.forename: Longzhu
authors.initials: L
authors.lastname: Cui
authors.affiliation: b Department of Bacteriology, School of Medicine, Juntendo University, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramatsu
authors.affiliation: e Department of Medical Microbiology and Immunology, Universiti Kebangsaan Malaysia, Malaysia.
authors.forename: Salasawati
authors.initials: S
authors.lastname: Hussin
authors.affiliation: a UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Malaysia.
authors.forename: Rahman
authors.initials: R
authors.lastname: Jamal
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001120:Arginine / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D020543:Proteome; D013203:Staphylococcal Infections; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D020543:Proteome; D014640:Vancomycin; D001120:Arginine; D006867:Hydrolases; C019723:arginine deiminase
keywords: ATP; Staphylococcus aureus de résistance intermédiaire à la vancomycine; ammonia; ammoniac; arginine catabolism; catabolisme de l’arginine; cell wall thickening; vancomycin-intermediate Staphylococcus aureus; épaississement de la paroi cellulaire