PDF(Pubmed)
Abstract：
Gonorrhea, which is caused by Neisseria gonorrhoeae, is the second most prevalent sexually transmitted infection worldwide. The increasing appearance of isolates that are resistant to approved therapeutics raises the concern that gonorrhea may become untreatable. Here, we serendipitously identified oxydifficidin as a potent N. gonorrhoeae antibiotic through the observation of a Bacillus amyloliquefaciens contaminant in a lawn of N. gonorrhoeae. Oxydifficidin is active against both wild-type and multidrug-resistant N. gonorrhoeae. It\'s potent activity results from a combination of DedA-assisted uptake into the cytoplasm and the presence of an oxydifficidin-sensitive ribosomal protein L7/L12 (RplL). Our data indicates that oxydifficidin binds to the ribosome at a site that is distinct from other antibiotics and that L7/L12 is uniquely associated with its mode of action. This study opens a potential new avenue for addressing antibiotic resistant gonorrhea and underscores the possibility of identifying overlooked natural products from cultured bacteria, particularly those with activity against previously understudied pathogens.
摘要：
淋病,是由淋病奈瑟菌引起的,是全球第二大流行的性传播感染。对批准的治疗剂具有抗性的分离株的出现增加了淋病可能变得无法治疗的担忧。这里,我们通过在淋病奈瑟菌草坪中观察解淀粉芽孢杆菌污染物，偶然发现了羟二异嘧啶是一种有效的淋病奈瑟菌抗生素。氧二吡嗪对野生型和耐多药淋病奈瑟菌都有活性。它的有效活性是由DedA辅助摄取到细胞质中和存在氧二吡嗪敏感核糖体蛋白L7/L12（RplL）的组合产生的。我们的数据表明，氧二吡嗪在与其他抗生素不同的位点与核糖体结合，并且L7/L12与其作用方式独特相关。这项研究为解决抗生素耐药性淋病开辟了一条潜在的新途径，并强调了从培养细菌中识别被忽视的天然产物的可能性。特别是那些对以前研究不足的病原体有活性的。
