{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:16:35Z","timestamp":1785428195284,"version":"3.56.0"},"reference-count":58,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for the Support of Research and Scientific and Technological Development of Maranh\u00e3o","award":["ACT-02510\/23"],"award-info":[{"award-number":["ACT-02510\/23"]}]},{"name":"Foundation for the Support of Research and Scientific and Technological Development of Maranh\u00e3o","award":["BEPP-02457\/23"],"award-info":[{"award-number":["BEPP-02457\/23"]}]},{"name":"Foundation for the Support of Research and Scientific and Technological Development of Maranh\u00e3o","award":["Universal-06536\/22"],"award-info":[{"award-number":["Universal-06536\/22"]}]},{"name":"Foundation for the Support of Research and Scientific and Technological Development of Maranh\u00e3o","award":["PQ-C-12482\/25"],"award-info":[{"award-number":["PQ-C-12482\/25"]}]},{"name":"Foundation for the Support of Research and Scientific and Technological Development of Maranh\u00e3o","award":["PPSUS-609\/25"],"award-info":[{"award-number":["PPSUS-609\/25"]}]},{"award":["ACT-02510\/23"],"award-info":[{"award-number":["ACT-02510\/23"]}],"id":[{"id":"https:\/\/ror.org\/03vqm2n93","id-type":"ROR","asserted-by":"publisher"}]},{"award":["BEPP-02457\/23"],"award-info":[{"award-number":["BEPP-02457\/23"]}],"id":[{"id":"https:\/\/ror.org\/03vqm2n93","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Universal-06536\/22"],"award-info":[{"award-number":["Universal-06536\/22"]}],"id":[{"id":"https:\/\/ror.org\/03vqm2n93","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PQ-C-12482\/25"],"award-info":[{"award-number":["PQ-C-12482\/25"]}],"id":[{"id":"https:\/\/ror.org\/03vqm2n93","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PPSUS-609\/25"],"award-info":[{"award-number":["PPSUS-609\/25"]}],"id":[{"id":"https:\/\/ror.org\/03vqm2n93","id-type":"ROR","asserted-by":"publisher"}]},{"name":"CEUMA University"},{"id":[{"id":"https:\/\/ror.org\/044g0p936","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mycobacterium abscessus subsp. massiliense (Mabs) is an emerging nontuberculous mycobacterium associated with difficult-to-treat infections due to intrinsic antimicrobial resistance, intracellular persistence, biofilm formation, and limited responsiveness to currently available therapeutic regimens. In this context, adjuvant strategies targeting iron-dependent metabolic pathways and metal homeostasis may enhance the efficacy of conventional antimicrobials. This study investigated deferoxamine (DFO), a clinically approved iron chelator, as a potential adjuvant against Mabs using integrated in vitro and in silico approaches. Cytocompatibility was assessed using an MTT assay in RAW 264.7 macrophages and a hemolysis assay in human erythrocytes. Antimicrobial activity was evaluated through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, while interactions with clarithromycin (CLA) and amikacin (AMK) were assessed using the checkerboard method. Effects on virulence-associated phenotypes were examined through biofilm formation assays and protein quantification in extracellular vesicle-enriched fractions. Intracellular activity and modulation of inflammatory mediator gene expression were investigated in Mabs-infected RAW 264.7 macrophages through colony-forming unit (CFU) recovery and reverse transcription quantitative polymerase chain reaction (qPCR). DFO exhibited low cytotoxicity and negligible hemolytic activity under the tested conditions. Direct antimicrobial testing revealed a predominantly bacteriostatic profile (MIC = 9.75 \u00b5g\/mL; MBC &gt; 10 mg\/mL), whereas checkerboard analysis suggested a synergistic interaction with CLA (FICI = 0.047), which requires further confirmation by time-kill or CFU-based combination assays. Furthermore, DFO reduced biofilm biomass, decreased protein levels in vesicle-enriched fractions, lowered intracellular bacterial burden, and modulated cytokine gene expression in infected macrophages. Molecular docking, ADME\/Tox, and PASS analyses generated exploratory hypotheses regarding potential molecular interactions and pharmacological properties. Overall, these findings support DFO as a promising experimental adjuvant candidate for further investigation against Mabs, particularly in combination with clarithromycin. However, confirmation of a putative iron-restriction-associated mechanism and its translational relevance will require validation in additional clinical isolates, iron-rescue experiments, mature biofilm models, and in vivo studies.<\/jats:p>","DOI":"10.3390\/ijms27135789","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"5789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deferoxamine Exhibits Antimicrobial and Immunomodulatory Activity Against Mycobacterium abscessus: Integrated In Silico and In Vitro Evidence"],"prefix":"10.3390","volume":"27","author":[{"given":"Roseane Lustosa de Santana","family":"Lira","sequence":"first","affiliation":[{"name":"Postgraduate Program in Health Sciences, Federal University of Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2875-1837","authenticated-orcid":false,"given":"Fabiane Barbosa","family":"Mendes","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biosciences Applied to Health, CEUMA University\u2014UNICEUMA, S\u00e3o Lu\u00eds 65075-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2872-7107","authenticated-orcid":false,"given":"Pedro Lucas Brito Tromps","family":"Roxo","sequence":"additional","affiliation":[{"name":"Medical School, CEUMA University\u2014UNICEUMA, S\u00e3o Lu\u00eds 65075-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana Ten\u00f3rio Albuquerque Madruga Mesquita Meireles","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Medical School, CEUMA University\u2014UNICEUMA, S\u00e3o Lu\u00eds 65075-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio C\u00e9sar Santana","family":"de Azevedo","sequence":"additional","affiliation":[{"name":"Medical School, CEUMA University\u2014UNICEUMA, S\u00e3o Lu\u00eds 65075-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ar\u00edcia de Azevedo","family":"Vidigal","sequence":"additional","affiliation":[{"name":"Medical School, CEUMA University\u2014UNICEUMA, S\u00e3o Lu\u00eds 65075-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleon\u00f4ra Costa Monteiro","family":"Gimenes","sequence":"additional","affiliation":[{"name":"Medical School, CEUMA University\u2014UNICEUMA, S\u00e3o Lu\u00eds 65075-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reidson Stanley Soares","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Dentistry, CEUMA University\u2014UNICEUMA, S\u00e3o Lu\u00eds 65075-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivaldo Lira","family":"Filho","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Federal University of Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Evangelista Carnib","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Federal University of Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7771-8369","authenticated-orcid":false,"given":"Fl\u00e1via Danyelle Oliveira","family":"Nunes","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Federal University of Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayane Cristina Pereira","family":"Marques","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Federal University of Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7163-3831","authenticated-orcid":false,"given":"Jos\u00e9 Lima","family":"Pereira-Filho","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Federal University of Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7723-0662","authenticated-orcid":false,"given":"Carmem Duarte Lima","family":"Campos","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Federal University of Maranh\u00e3o\u2014UFMA, S\u00e3o Lu\u00eds 65080-805, 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