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Overcoming antibiotic resistance involves several strategies, including the inhibition of resistance mechanisms. Among the various resistance mechanisms, aminoglycoside phosphotransferases (APHs) catalyze the transfer of the \u03b3-phosphate from a nucleotide donor to various aminoglycosides, leading to their inactivation. In this work, using a fragment-based drug design (FBDD) approach, we have identified and characterized a promising APH inhibitor capable of increasing the sensitivity of\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    and\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    resistant to aminoglycosides. It is therefore a good candidate for the future development of APH inhibitors to be prescribed in combination with aminoglycosides. This molecule is a competitive inhibitor of adenosine 5\u2019-triphosphate (ATP), the phosphate donor of APHs. Further studies are required to optimize this molecule to improve its specificity for APHs and its bioavailability in bacteria.\n                  <\/jats:p>","DOI":"10.1038\/s42004-025-01795-6","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T13:57:24Z","timestamp":1764251844000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fragment-based drug design of a bacterial kinase inhibitor capable of increasing the antibiotic sensitivity of clinical isolates"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4042-8145","authenticated-orcid":false,"given":"Julien","family":"Kowalewski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Deutscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Richardoz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Tomaszczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Gelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Labesse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3710-8838","authenticated-orcid":false,"given":"Felix","family":"Hausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9129-7131","authenticated-orcid":false,"given":"Gerard D.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Dunyach-Remy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Guichou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6348-5311","authenticated-orcid":false,"given":"Corinne","family":"Lionne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"1795_CR1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.bcp.2016.10.001","volume":"133","author":"R Aminov","year":"2017","unstructured":"Aminov, R. 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