{"title":"Zap the clap with DNA: a novel microbicide for preventing <i>Neisseria gonorrhoeae</i> infection.","authors":"Maria A Rendon, Magdalene So","doi":"10.1128/aac.00794-24","DOIUrl":null,"url":null,"abstract":"<p><p>Each year, <i>Neisseria gonorrhoeae</i> (Ngo) causes over 1.5 million new infections in the United States, and >87 million worldwide. The absence of a vaccine for preventing gonorrhea, the rapid emergence of multidrug-resistant and extremely drug-resistant Ngo strains, and the limited number of antibiotics available for treating gonorrhea underscore the importance of developing new modalities for addressing Ngo infection. Here, we describe DNA-based microbicides that kill Ngo but not commensals. Previously, we showed that Ngo is killed when it takes up differentially methylated DNA with homology to its genome. We exploited this Achilles heel to develop a new class of microbicides for preventing Ngo infection. These microbicides consist of DNA molecules with specific sequences and a methylation pattern different from Ngo DNA. These DNAs kill low-passage and antibiotic-resistant clinical isolates with high efficiency but leave commensals unharmed. Equally important, the DNAs are equally effective against Ngo whether they are in buffered media or personal lubricants. These findings illustrate the potential of this new class of practical, low-cost, self-administered DNA-based microbicides for preventing Ngo transmission during sexual intercourse.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antimicrobial Agents and Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1128/aac.00794-24","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Each year, Neisseria gonorrhoeae (Ngo) causes over 1.5 million new infections in the United States, and >87 million worldwide. The absence of a vaccine for preventing gonorrhea, the rapid emergence of multidrug-resistant and extremely drug-resistant Ngo strains, and the limited number of antibiotics available for treating gonorrhea underscore the importance of developing new modalities for addressing Ngo infection. Here, we describe DNA-based microbicides that kill Ngo but not commensals. Previously, we showed that Ngo is killed when it takes up differentially methylated DNA with homology to its genome. We exploited this Achilles heel to develop a new class of microbicides for preventing Ngo infection. These microbicides consist of DNA molecules with specific sequences and a methylation pattern different from Ngo DNA. These DNAs kill low-passage and antibiotic-resistant clinical isolates with high efficiency but leave commensals unharmed. Equally important, the DNAs are equally effective against Ngo whether they are in buffered media or personal lubricants. These findings illustrate the potential of this new class of practical, low-cost, self-administered DNA-based microbicides for preventing Ngo transmission during sexual intercourse.
每年,淋病奈瑟菌(Ngo)在美国造成的新感染人数超过 150 万,在全球则超过 8700 万。由于缺乏预防淋病的疫苗,耐多药和极度耐药的淋病奈瑟菌株迅速出现,以及可用于治疗淋病的抗生素数量有限,这一切都凸显了开发新方法解决淋病奈瑟菌感染问题的重要性。在这里,我们介绍了基于 DNA 的杀微生物剂,它能杀死 Ngo,但不能杀死共生菌。此前,我们曾发现,当 Ngo 吸收与其基因组同源的不同甲基化 DNA 时,就会被杀死。我们利用这一致命弱点开发出了一类新型杀微生物剂,用于预防 Ngo 感染。这些杀微生物剂由具有特定序列和不同于 Ngo DNA 甲基化模式的 DNA 分子组成。这些 DNA 能高效杀死低通过率和抗生素耐药的临床分离株,而对共生菌则毫发无损。同样重要的是,无论是在缓冲介质中还是在个人润滑剂中,DNA 对 Ngo 都同样有效。这些研究结果表明,这种基于 DNA 的新型杀微生物剂是一种实用、低成本、可自控的杀微生物剂,具有预防性交过程中 Ngo 传播的潜力。
期刊介绍:
Antimicrobial Agents and Chemotherapy (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.