Activated ADI pathway: the initiator of intermediate vancomycin resistance in Staphylococcus aureus

• Published in: Canadian journal of microbiology Vol. 63; no. 3; pp. 260 - 264
• Main Authors: Tan, Xin-Ee, Neoh, Hui-min, Looi, Mee-Lee, Chin, Siok Fong, Cui, Longzhu, Hiramatsu, Keiichi, Hussin, Salasawati, Jamal, Rahman
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.03.2017; Canadian Science Publishing NRC Research Press
• Subjects: Ammonia; ammoniac; Anti-Bacterial Agents - pharmacology; Antibiotics; Arginine; Arginine - metabolism; arginine catabolism; ATP; Bacterial Proteins - genetics; Biosynthesis; Catabolism; catabolisme de l’arginine; cell wall thickening; Drug resistance; Enzyme Activation; Gene Expression Profiling; Genetic aspects; Humans; Hydrolases - metabolism; Microbial drug resistance; Microbial Sensitivity Tests; Microbiological research; Molecules; Mutation; Physiological aspects; Proteome; Proteomics; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - enzymology; Staphylococcus aureus - genetics; Staphylococcus aureus de résistance intermédiaire à la vancomycine; Staphylococcus infections; Vancomycin; Vancomycin - pharmacology; Vancomycin Resistance - genetics; vancomycin-intermediate Staphylococcus aureus; épaississement de la paroi cellulaire; Canada; ammoniac; vancomycin-intermediate Staphylococcus aureus; cell wall thickening; arginine catabolism; ammonia; épaississement de la paroi cellulaire; catabolisme de l’arginine; ATP; Staphylococcus aureus de résistance intermédiaire à la vancomycine
• ISSN: 0008-4166; 1480-3275
• DOI: 10.1139/cjm-2016-0439

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.