{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:48:04Z","timestamp":1792187284928,"version":"4.4.0"},"reference-count":80,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003336","name":"Bulgarian National Science Fund","doi-asserted-by":"publisher","award":["KP\u221206-M69\/01"],"award-info":[{"award-number":["KP\u221206-M69\/01"]}],"id":[{"id":"10.13039\/501100003336","id-type":"DOI","asserted-by":"publisher"}]},{"name":"L\u2019Oreal","award":["KP\u221206-M69\/01"],"award-info":[{"award-number":["KP\u221206-M69\/01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The emergence of multidrug-resistant (MDR) microorganisms combined with the ever-draining antibiotic pipeline poses a disturbing and immensely growing public health challenge that requires a multidisciplinary approach and the application of novel therapies aimed at unconventional targets and\/or applying innovative drug formulations. Hence, bacterial iron acquisition systems and bacterial Fe2+\/3+-containing enzymes have been identified as a plausible target of great potential. The intriguing \u201cTrojan horse\u201d approach deprives microorganisms from the essential iron. Recently, gallium\u2019s potential in medicine as an iron mimicry species has attracted vast attention. Different Ga3+ formulations exhibit diverse effects upon entering the cell and thus supposedly have multiple targets. The aim of the current study is to specifically distinguish characteristics of great significance in regard to the initial gallium-based complex, allowing the alien cation to effectively compete with the native ferric ion for binding the siderophores pyochelin and pyoverdine secreted by the bacterium P. aeruginosa. Therefore, three gallium-based formulations were taken into consideration: the first-generation gallium nitrate, Ga(NO3)3, metabolized to Ga3+-hydrated forms, the second-generation gallium maltolate (tris(3-hydroxy-2-methyl-4-pyronato)gallium), and the experimentally proven Ga carrier in the bloodstream\u2014the protein transferrin. We employed a reliable in silico approach based on DFT computations in order to understand the underlying biochemical processes that govern the Ga3+\/Fe3+ rivalry for binding the two bacterial siderophores.<\/jats:p>","DOI":"10.3390\/biom14040487","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T08:22:44Z","timestamp":1713342164000},"page":"487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["In Silico Analysis of the Ga3+\/Fe3+ Competition for Binding the Iron-Scavenging Siderophores of P. aeruginosa\u2014Implementation of Three Gallium-Based Complexes in the \u201cTrojan Horse\u201d Antibacterial Strategy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6645-8319","authenticated-orcid":false,"given":"Nikoleta","family":"Kircheva","sequence":"first","affiliation":[{"name":"Institute of Optical Materials and Technologies \u201cAcad. J. Malinowski\u201d, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Dobrev","sequence":"additional","affiliation":[{"name":"Institute of Optical Materials and Technologies \u201cAcad. J. Malinowski\u201d, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0887-4610","authenticated-orcid":false,"given":"Vladislava","family":"Petkova","sequence":"additional","affiliation":[{"name":"Institute of Optical Materials and Technologies \u201cAcad. J. Malinowski\u201d, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyubima","family":"Yocheva","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Pharmacy, Sofia University \u201cSt. Kliment Ohridski\u201d, 1164 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4717-8028","authenticated-orcid":false,"given":"Silvia","family":"Angelova","sequence":"additional","affiliation":[{"name":"Institute of Optical Materials and Technologies \u201cAcad. J. Malinowski\u201d, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"},{"name":"University of Chemical Technology and Metallurgy, 1756 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todor","family":"Dudev","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Pharmacy, Sofia University \u201cSt. Kliment Ohridski\u201d, 1164 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"ref_1","first-page":"277","article-title":"The Antibiotic Resistance Crisis Part 1: Causes and Threats","volume":"40","author":"Ventola","year":"2015","journal-title":"Pharm. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S122","DOI":"10.1038\/nm1145","article-title":"Antibacterial Resistance Worldwide: Causes, Challenges and Responses","volume":"10","author":"Levy","year":"2004","journal-title":"Nat. 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