Arginine catabolic mobile element encoded speG abrogates the unique hypersensitivity of Staphylococcus aureus to exogenous polyamines.

Arginine catabolic mobile element encoded speG abrogates the unique hypersensitivity of Staphylococcus aureus to exogenous polyamines.
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DOI:
10.1111/j.1365-2958.2011.07809.x
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发表时间:
2011-10
影响因子:
3.6
通讯作者:
Richardson AR
Richardson AR
中科院分区:
生物学2区
文献类型:
--
作者:
Joshi GS;Spontak JS;Klapper DG;Richardson AR

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多胺,包括精胺(Spm)和亚精胺(Spd),是脂肪族阳离子,据报道由所有生物体合成。它们对细胞发挥多效性作用,并且是有效的核酸和蛋白质合成所必需的。在这里,我们报告说,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或其前体化合物腐胺和胍丁胺。此外,虽然补充含有多胺的成分确定的培养基通常促进细菌生长,但Spm和Spd对S.生理浓度的金黄色葡萄球菌。特别缺乏甲基萘醌生物合成的小菌落变体出现后,长期的SPM曝光,并表现出降低多胺的敏感性。然而,其他有缺陷的突变体对SPM的敏感性也不低,这意味着甲基萘醌本身而不是一般的呼吸作用是完整的SPM毒性所必需的。多胺超敏反应区分S。金黄色葡萄球菌与其他细菌的差异,并且除了属于USA-300组的社区相关耐甲氧西林金黄色葡萄球菌(CA-MRSA)的菌株外,所有测试菌株都表现出这种差异。我们在USA-300特异性精氨酸分解代谢移动的元件(ACME)中鉴定了一个编码Spm/Spd N-乙酰基转移酶的基因,该酶是多胺抗性所必需和充分的。S.金黄色葡萄球菌在感染过程中遇到显著的多胺水平,然而ACME编码的speG的获得允许USA-300克隆规避多胺超敏性,这是S.金黄色。
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.
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