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PPBI-POCI-01-0145-FEDER-022122","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"research infrastructure PPBI-POCI-01-0145-FEDER-022122","award":["2022.03627.PTDC"],"award-info":[{"award-number":["2022.03627.PTDC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Methicillin-resistant Staphylococcus aureus (M RSA) infections, in particular biofilm-organized bacteria, remain a clinical challenge and a serious health problem. Rifabutin (RFB), an antibiotic of the rifamycins class, has shown in previous work excellent anti-staphylococcal activity. Here, we proposed to load RFB in liposomes aiming to promote the accumulation of RFB at infected sites and consequently enhance the therapeutic potency. Two clinical isolates of MRSA, MRSA-C1 and MRSA-C2, were used to test the developed formulations, as well as the positive control, vancomycin (VCM). RFB in free and liposomal forms displayed high antibacterial activity, with similar potency between tested formulations. In MRSA-C1, minimal inhibitory concentrations (MIC) for Free RFB and liposomal RFB were 0.009 and 0.013 \u03bcg\/mL, respectively. Minimum biofilm inhibitory concentrations able to inhibit 50% biofilm growth (MBIC50) for Free RFB and liposomal RFB against MRSA-C1 were 0.012 and 0.008 \u03bcg\/mL, respectively. Confocal microscopy studies demonstrated the rapid internalization of unloaded and RFB-loaded liposomes in the bacterial biofilm matrix. In murine models of systemic MRSA-C1 infection, Balb\/c mice were treated with RFB formulations and VCM at 20 and 40 mg\/kg of body weight, respectively. The in vivo results demonstrated a significant reduction in bacterial burden and growth index in major organs of mice treated with RFB formulations, as compared to Control and VCM (positive control) groups. Furthermore, the VCM therapeutic dose was two fold higher than the one used for RFB formulations, reinforcing the therapeutic potency of the proposed strategy. In addition, RFB formulations were the only formulations associated with 100% survival. Globally, this study emphasizes the potential of RFB nanoformulations as an effective and safe approach against MRSA infections.<\/jats:p>","DOI":"10.3390\/ph17040470","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T10:11:55Z","timestamp":1712571115000},"page":"470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Liposomal Rifabutin\u2014A Promising Antibiotic Repurposing Strategy against Methicillin-Resistant Staphylococcus aureus Infections"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7725-4701","authenticated-orcid":false,"given":"Jacinta O.","family":"Pinho","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Magda","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"Center for Interdisciplinary Research in Animal Health (CIISA), Faculty of Veterinary Medicine, Universidade de Lisboa, 1300-477 Lisboa, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Faculty of Veterinary Medicine, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8168-7267","authenticated-orcid":false,"given":"Mariana","family":"Coelho","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-9459","authenticated-orcid":false,"given":"Sandra N.","family":"Pinto","sequence":"additional","affiliation":[{"name":"iBB-Institute for Bioengineering and Biosciences and Associate Laboratory i4HB\u2212Institute for Health and Bioeconomy at Department of Bioengineering, Instituto SuperiorT\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}]},{"given":"Sandra I.","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Research in Animal Health (CIISA), Faculty of Veterinary Medicine, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6814-7226","authenticated-orcid":false,"given":"Maria Manuela","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"IBEB, Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1080\/14760584.2016.1179583","article-title":"Staphylococcus aureus: The current state of disease, pathophysiology and strategies for prevention","volume":"15","author":"Dayan","year":"2016","journal-title":"Expert Rev. Vaccines"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1111\/j.1444-0903.2005.00977.x","article-title":"Diagnosis and management of Staphylococcus aureus bacteraemia","volume":"35","author":"Mitchell","year":"2005","journal-title":"Intern. Med. 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