Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA-assisted uptake and ribosomal protein RplL sensitivity
Gonorrhea, which is caused by Neisseria gonorrhoeae, is the second most reported 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 o...
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eLife Sciences Publications Ltd
2025-05-01
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| Online Access: | https://elifesciences.org/articles/99281 |
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| author | Jingbo Kan Adrian Morales-Amador Yozen Hernandez Melinda A Ternei Christophe Lemetre Logan W Maclntyre Nicolas Biais Sean F Brady |
| author_facet | Jingbo Kan Adrian Morales-Amador Yozen Hernandez Melinda A Ternei Christophe Lemetre Logan W Maclntyre Nicolas Biais Sean F Brady |
| author_sort | Jingbo Kan |
| collection | DOAJ |
| description | Gonorrhea, which is caused by Neisseria gonorrhoeae, is the second most reported 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. Its 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 indicate 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. |
| format | Article |
| id | doaj-art-6d7e27b44cf34471a95e2b067d2e18e2 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-6d7e27b44cf34471a95e2b067d2e18e22025-08-20T02:38:22ZengeLife Sciences Publications LtdeLife2050-084X2025-05-011310.7554/eLife.99281Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA-assisted uptake and ribosomal protein RplL sensitivityJingbo Kan0https://orcid.org/0009-0006-1917-6577Adrian Morales-Amador1https://orcid.org/0000-0001-7944-308XYozen Hernandez2https://orcid.org/0000-0003-3349-8856Melinda A Ternei3Christophe Lemetre4Logan W Maclntyre5Nicolas Biais6https://orcid.org/0009-0004-6054-594XSean F Brady7https://orcid.org/0000-0001-5967-8586Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, United States; Graduate Center, City University of New York, New York City, United States; Brooklyn College, City University of New York, New York, United StatesLaboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, United StatesLaboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, United StatesLaboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, United StatesLaboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, United StatesLaboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, United StatesGraduate Center, City University of New York, New York City, United States; Brooklyn College, City University of New York, New York, United States; Laboratoire Jean Perrin, UMR 8237 Sorbonne Université/CNRS, Paris, FranceLaboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, United StatesGonorrhea, which is caused by Neisseria gonorrhoeae, is the second most reported 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. Its 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 indicate 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.https://elifesciences.org/articles/99281Neisseria gonorrhoeaecell cultureantibiotics |
| spellingShingle | Jingbo Kan Adrian Morales-Amador Yozen Hernandez Melinda A Ternei Christophe Lemetre Logan W Maclntyre Nicolas Biais Sean F Brady Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA-assisted uptake and ribosomal protein RplL sensitivity eLife Neisseria gonorrhoeae cell culture antibiotics |
| title | Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA-assisted uptake and ribosomal protein RplL sensitivity |
| title_full | Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA-assisted uptake and ribosomal protein RplL sensitivity |
| title_fullStr | Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA-assisted uptake and ribosomal protein RplL sensitivity |
| title_full_unstemmed | Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA-assisted uptake and ribosomal protein RplL sensitivity |
| title_short | Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA-assisted uptake and ribosomal protein RplL sensitivity |
| title_sort | oxydifficidin a potent neisseria gonorrhoeae antibiotic due to deda assisted uptake and ribosomal protein rpll sensitivity |
| topic | Neisseria gonorrhoeae cell culture antibiotics |
| url | https://elifesciences.org/articles/99281 |
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