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The Human Microbiome as a Focus of Antibiotic Discovery: Neisseria mucosa Displays Activity Against Neisseria gonorrhoeae
Frontiers in Microbiology ( IF 4.0 ) Pub Date : 2020-11-09 , DOI: 10.3389/fmicb.2020.577762
Ellen L. Aho , Jenie M. Ogle , Anna M. Finck

Neisseria gonorrhoeae infections are a serious global health problem. This organism has developed disturbing levels of antibiotic resistance, resulting in the need for new approaches to prevent and treat gonorrhea. The genus Neisseria also includes several members of the human microbiome that live in close association with an array of microbial partners in a variety of niches. We designed an undergraduate antibiotic discovery project to examine a panel of nonpathogenic Neisseria species for their ability to produce antimicrobial secondary metabolites. Five strains belonging to the N. mucosa species group displayed activity against other Neisseria in delayed antagonism assays; three of these were active against N. gonorrhoeae. The antimicrobial compound secreted by N. mucosa NRL 9300 remained active in the presence of catalase, trypsin, and HEPES buffer, and effectively inhibited a DNA uptake mutant of N. gonorrhoeae. Antimicrobial activity was also retained in an ethyl acetate extract of plate grown N. mucosa NRL 9300. These data suggest N. mucosa produces an antimicrobial secondary metabolite that is distinct from previously described antigonococcal agents. This work also serves as a demonstration project that could easily be adapted to studying other members of the human microbiome in undergraduate settings. We offer the perspective that both introductory and more advanced course-based and apprentice-style antibiotic discovery projects focused on the microbiome have the potential to enrich undergraduate curricula and we describe transferrable techniques and strategies to facilitate project design.



中文翻译:

人类微生物组作为抗生素发现的重点:奈瑟氏菌粘膜显示针对淋病奈瑟氏菌的活性

淋球菌感染是严重的全球健康问题。这种生物体已产生令人不安的抗生素抗性水平,因此需要预防和治疗淋病的新方法。属奈瑟氏菌还包括人类微生物组的几个成员,这些成员与各种生态位中的一系列微生物伴侣密切相关。我们设计了一个本科生抗生素发现项目来检查一组非致病性奈瑟氏菌种产生抗菌次级代谢产物的能力。五种属于N.黏膜 物种组表现出针对其他物种的活动 奈瑟氏菌在延迟拮抗试验中 其中三个积极反对淋病奈瑟菌。分泌的抗菌化合物N.黏膜 NRL 9300在过氧化氢酶,胰蛋白酶和HEPES缓冲液的存在下仍保持活性,并有效抑制DNA的DNA吸收突变体 淋病奈瑟菌。抗菌活性也保留在平板培养的乙酸乙酯提取物中N.黏膜 NRL9300。这些数据表明 N.黏膜产生抗微生物的次级代谢产物,与先前描述的抗性淋球菌药物不同。这项工作还可以作为一个示范项目,可以很容易地应用于在大学环境中研究人类微生物组的其他成员。我们提供的观点是,针对微生物组的入门级和更高级的以课程为基础的学徒型抗生素发现项目都具有丰富本科课程的潜力,并且我们描述了可转让的技术和策略来促进项目设计。

更新日期:2020-12-03
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