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2
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Infect Dis Ther. 2023 Sep;12(9):2307-2320. doi: 10.1007/s40121-023-00862-6. Epub 2023 Sep 26.
3
GyrB in silico mining in 27 151 global gonococcal genomes from 1928-2021 combined with zoliflodacin in vitro testing of 71 international gonococcal isolates with different GyrB, ParC and ParE substitutions confirms high susceptibility.对1928年至2021年全球27151株淋球菌基因组进行GyrB的电子挖掘,并结合对71株具有不同GyrB、ParC和ParE替代的国际淋球菌分离株进行的佐利氟达辛体外测试,证实了高敏感性。
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用 DNA 消灭淋病:一种新型杀微生物剂预防 感染。

Zap the clap with DNA: a novel microbicide for preventing infection.

机构信息

Department of Immunobiology, the BIO5 Institute, University of Arizona, Tucson, Arizona, USA.

出版信息

Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0079424. doi: 10.1128/aac.00794-24. Epub 2024 Aug 16.

DOI:10.1128/aac.00794-24
PMID:39150247
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11459949/
Abstract

Each year, (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.

摘要

每年,(淋病奈瑟菌)在美国导致超过 150 万例新感染,在全球导致超过 8700 万例。目前尚无预防淋病的疫苗,淋病奈瑟菌对抗菌药物的耐药性迅速出现,且可用于治疗淋病的抗生素数量有限,这些因素都强调了开发新方法来解决淋病奈瑟菌感染问题的重要性。在这里,我们描述了可杀死淋病奈瑟菌但不伤害共生菌的基于 DNA 的杀微生物剂。此前,我们已经表明,当淋病奈瑟菌摄取与其基因组具有同源性的差异甲基化 DNA 时,它会被杀死。我们利用这一致命弱点开发了一种新的预防淋病奈瑟菌感染的杀微生物剂。这些杀微生物剂由具有特定序列和甲基化模式的 DNA 分子组成,与淋病奈瑟菌 DNA 不同。这些 DNA 可以高效杀死低传代和耐药的临床分离株,但不会伤害共生菌。同样重要的是,这些 DNA 在缓冲介质或个人润滑剂中对淋病奈瑟菌同样有效。这些发现表明,这种新型实用、低成本、可自我管理的基于 DNA 的杀微生物剂具有预防性交期间淋病奈瑟菌传播的潜力。