Chemical Modification and Detoxification of the Pseudomonas aeruginosa Toxin 2-Heptyl-4-hydroxyquinoline N-Oxide by Environmental and Pathogenic Bacteria
Chemical Modification and Detoxification of the Pseudomonas aeruginosa Toxin 2-Heptyl-4-hydroxyquinoline N-Oxide by Environmental and Pathogenic Bacteria
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DOI：
10.1021/acschembio.7b00345
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发表时间：
2017-09-01
影响因子：
4
通讯作者：
Fetzner, Susanne
中科院分区：
文献类型：
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作者：
Thierbach, Sven;Birmes, Franziska S.;Fetzner, Susanne
2-庚基-4-羟基喹啉 N-氧化物 (HQNO) 是机会性病原体铜绿假单胞菌产生的主要次级代谢产物和毒力因子，可作为呼吸电子转移的有效抑制剂，从而影响宿主细胞和微生物。在这项研究中，我们证明了环境和病原细菌以前未知的转化和解毒这种化合物的能力。节杆菌属和红球菌属菌株。金黄色葡萄球菌在 HQNO 的 C-3 处引入了羟基，而脓肿分枝杆菌、偶发分枝杆菌和耻垢分枝杆菌则在 HQNO 的 C-3 处引入了羟基。进行 O-甲基化，形成 2-hepty1-1-inethoxy-4-okoquin.Oline 作为初始代谢物。芽孢杆菌属产生糖基化衍生物 2-hepty1-1-(beta-D-glucopyranosydy1)-4-oxoquinoline。分析这些代谢物对细胞呼吸和膜组分对苯二酚氧化酶活性的影响表明，它们的 EC50 值比 HQNO 高出多个数量级：此外，代谢物优先时的细胞活性氧水平显着低于 HQNO 影响下的活性氧水平。因此，转化 HQNO 的能力应该会带来针对铜绿假单胞菌的竞争优势。我们的研究结果为细菌的代谢多样性提供了新的见解，并为代谢相互作用增加了另一层复杂性，这可能有助于塑造包含铜绿假单胞菌的多微生物群落。
2-Heptyl-4-hydroxyquinoline N-oxide (HQNO), a major secondary metabolite and virulence factor produced by the.opportunistic pathogen Pseudomonas aeruginosa, acts as a potent inhibitor of-respiratory electron transfer and thereby affects host cells as well as microorganisms. In this study, we demonstrate the previously unknown capability of environmental and pathogenic bacteria to transform and detoxify this compound. Strains of Arthrobacter and Rhodococcus spp. as well as Staphylococcus aureus introduced a hydroxyl group at C-3 of HQNO, whereas Mycobacterium abscessus, M. fortuiturn, and M.smegmatis. performed An O-methylation, forming 2-hepty1-1-inethoxy-4-okoquin.Oline as the initial metabolite. Bacillus spp. produced the glycosylated,derivative, 2-hepty1-1-(beta-D-glucopyranosydy1)-4-oxoquinoline. Assaying the effects of these metabolites on cellular respiration and on quinol oxidase activity of membrane fractions revealed that their EC50 values were up tot orders of magnitude higher than that of HQNO: Furthermore, cellular levels of reactive oxygen species were significantly lower in the preience of the metabolites than under the influence of HQNO. Therefore, the capacity to transform HQNO should lead to a competitive, advantage against P. aeruginosa, Our findings contribute new insight into the metabolic diversity of bacteria and add another layer of complexity to the metabolic interactions which likely contribute to shaping polymicrobial communities Comprising P. aeruginosa.