title: Arginine catabolic mobile element encoded speG abrogates the unique hypersensitivity of Staphylococcus aureus to exogenous polyamines.
abstract: Polyamines, including spermine (Spm) and spermidine (Spd), are aliphatic cations that are reportedly synthesized by all living organisms. They exert pleiotropic effects on cells and are required for efficient nucleic acid and protein synthesis. Here, we report that the human pathogen Staphylococcus aureus lacks identifiable polyamine biosynthetic genes, and consequently produces no Spm/Spd or their precursor compounds putrescine and agmatine. Moreover, while supplementing defined medium with polyamines generally enhances bacterial growth, Spm and Spd exert bactericidal effects on S. aureus at physiological concentrations. Small colony variants specifically lacking menaquinone biosynthesis arose after prolonged Spm exposure and exhibited reduced polyamine sensitivity. However, other respiratory-defective mutants were no less susceptible to Spm implying menaquinone itself rather than general respiration is required for full Spm toxicity. Polyamine hypersensitivity distinguishes S. aureus from other bacteria and is exhibited by all tested strains save those belonging to the USA-300 group of community-associated methicillin-resistant S. aureus (CA-MRSA). We identified one gene within the USA-300-specific arginine catabolic mobile element (ACME) encoding a Spm/Spd N-acetyltransferase that is necessary and sufficient for polyamine resistance. S. aureus encounters significant polyamine levels during infection; however, the acquisition of ACME encoded speG allows USA-300 clones to circumvent polyamine hypersensitivity, a peculiar trait of S. aureus.
authors: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Gauri S
authors: GS
authors: Joshi
authors: Jeffrey S
authors: JS
authors: Spontak
authors: David G
authors: DG
authors: Klapper
authors: Anthony R
authors: AR
authors: Richardson
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D013095:Spermidine / Q000378:metabolism* / Q000494:pharmacology; D013096:Spermine / Q000378:metabolism* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D001120:Arginine; D001426:Bacterial Proteins; D013095:Spermidine; D013096:Spermine; D000099228:Diamine N-Acetyltransferase