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 physiologic 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 Staphylococcus 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.

Role of Lipase from Community-Associated Methicillin-Resistant Staphylococcus aureus Strain USA300 in Hydrolyzing Triglycerides into Growth-Inhibitory Free Fatty Acids

“…Triolein, a triglyceride composed of glycerol and three molecules of oleic acid (C 18:1 cis-9) was evaluated first. Triolein is similar to trilinolein in the sense that the chains of the fatty acids esterified to glycerol are the same length (C 18 ), yet in trilinolein the fatty acid chains are diunsaturated (C 18:2 ), while they are monounsaturated (C 18:1 ) in triolein. A significant delay in growth was observed in the presence of triolein compared to when the cells were grown in TSB alone, although the delay was reproducibly not as severe as when the cells were grown in the presence of trilinolein (Fig.…”

“…Recent studies have indicated that the emergence and rapid geographic spread of USA300 were due, at least in part, to its enhanced ability to persist on human skin, which was attributed to a mobile genetic element that uniquely confers resistance of USA300 to toxic polyamines encountered on the skin, to which all other strains of S. aureus are sensitive (18,19). Nevertheless, S. aureus as a species is capable of colonizing humans and must also cope with other innate defense mechanisms of the skin, the foremost of which include the production and secretion of sebum by the sebaceous glands (20,21).…”

A Cleavage-potentiated Fragment of Tear Lacritin Is Bactericidal

“…Spermidine and putrescine are notably essential for virulence in Salmonella gallinarum (62) and in P. aeruginosa, where spermidine is necessary for expression of the type III secretion system that delivers virulence proteins into eukaryotic cells (63). This differs from S. aureus, which cannot produce spermine or spermidine or the precursors agmatine and putrescine (64). Guanosine was lower.…”

Communication is Key: Do Bacteria use a Universal ‘Language‘ to Spread Resistance?

“…They are found in almost all living organisms [4]. Polyamines are produced by nearly all bacteria, with rare exceptions such as Staphylococcus aureus strains to which some polyamines, namely spermidine and spermine, are toxic as they lack polyamine-detoxifying enzymes [5]. The most common bacterial polyamines are putrescine and spermidine [6].…”