Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Mol Microbiol. 2011 Oct;82(1):9-20. doi: 10.1111/j.1365-2958.2011.07809.x. Epub 2011 Sep 8.
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.
多胺，包括精胺（Spm）和亚精胺（Spd），是一类据称由所有生物合成的脂族阳离子。它们对细胞具有多种效应，并且是有效核酸和蛋白质合成所必需的。在这里，我们报告人类病原体金黄色葡萄球菌缺乏可识别的多胺生物合成基因，因此不产生 Spm/Spd 或它们的前体化合物腐胺和胍丁胺。此外，尽管在限定培养基中补充多胺通常会增强细菌的生长，但 Spm 和 Spd 在生理浓度下对金黄色葡萄球菌具有杀菌作用。在长时间暴露于 Spm 后，特别缺乏menaquinone 生物合成的小菌落变体出现，并表现出降低的多胺敏感性。然而，其他呼吸缺陷突变体对 Spm 的敏感性并没有降低，这意味着menaquinone 本身而不是一般呼吸是完全 Spm 毒性所必需的。多胺超敏反应将金黄色葡萄球菌与其他细菌区分开来，并且所有测试的菌株都表现出这种敏感性，除了属于社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）的 USA-300 组的菌株。我们在 USA-300 特异性精氨酸分解移动元件（ACME）内鉴定了一个基因，该基因编码 Spm/Spd N-乙酰转移酶，该酶对于多胺抗性是必需和充分的。金黄色葡萄球菌在感染过程中会遇到大量的多胺；然而，ACME 编码的 speG 的获得使 USA-300 克隆能够规避多胺超敏反应，这是金黄色葡萄球菌的一个奇特特征。
