Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms.
Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms.
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DOI：
10.1126/science.aag3180
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发表时间：
2017-01-13
期刊：
影响因子：
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通讯作者：
Newman DK
中科院分区：
文献类型：
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作者：
Costa KC;Glasser NR;Conway SJ;Newman DK
条件致病菌铜绿假单胞菌产生称为吩嗪的彩色氧化还原活性代谢物，其支撑生物膜的发展、毒力和临床结果。虽然吩嗪以多种形式存在，但研究最多的是绿脓菌素。在这里，我们描述了绿脓菌素脱甲基酶（PodA），一个迄今为止未知的蛋白质，氧化绿脓菌素甲基甲醛和减少吡嗪环通过一个不寻常的互变异构脱甲基反应。与DNA酶类似，用PodA处理破坏铜绿假单胞菌生物膜形成，表明干扰绿脓菌素依赖性细胞外DNA释放到基质中。PodA依赖的绿脓菌素去甲基化也限制了经历缺氧条件的已建立的生物膜聚集体种群。总之，这些结果表明，调节细胞外氧化还原活性代谢物可以影响生物膜的适应性。
The opportunistic pathogen Pseudomonas aeruginosa produces colorful redox-active metabolites called phenazines, which underpin biofilm development, virulence and clinical outcomes. Though phenazines exist in many forms, the best studied is pyocyanin. Here, we describe pyocyanin demethylase (PodA), a hitherto uncharacterized protein that oxidizes the pyocyanin methyl group to formaldehyde and reduces the pyrazine ring via an unusual tautomerizing demethylation reaction. Treatment with PodA disrupts P. aeruginosa biofilm formation similarly to DNase, suggesting interference with the pyocyanin-dependent release of extracellular DNA into the matrix. PodA-dependent pyocyanin demethylation also restricts established biofilm aggregate populations experiencing anoxic conditions. Together, these results show that modulating extracellular redox-active metabolites can influence the fitness of biofilms.