Recapitulating Therapeutic Failure in Human Brucellosis: A PBMC- Based Model for Intracellular Brucella melitensi
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| Autori: | , , , , , , , , , , , , |
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| Format: | artículo original |
| Status: | Versión publicada |
| Datum izdanja: | 2026 |
| Opis: | Human brucellosis is one of the most prevalent bacterial zoonoses worldwide, caused by Brucella spp., a facultative intracellular pathogen. Among the species, B. melitensis is considered the most virulent and infectious for humans. Despite prolonged antibiotic regimens, 5–15% of patients experience relapse, and the underlying mechanisms of therapeutic failure remain poorly understood. We previously demonstrated that B. abortus can persist in a murine cell line model following antibiotic treatment, retaining its infectious potential. This finding suggested the presence of an intracellular reservoir that may contribute to reinfection and relapse. Building on this, we initiated a clinical study to investigate B. melitensis cellular associations in blood samples from patients with brucellosis. Among 19 Brucell a-positive cases—confirmed via blood culture, serology, and qPCR—two samples also tested positive for Brucella in the white blood cell (WBC) fraction using flow cytometry. The infected cell populations were heterogeneous, including both peripheral blood mononuclear cells (PBMCs) and granulocytes. Based on these findings, we developed a PBMC-based infection model using a B. melitensis strain engineered with a dual-color reporter system to monitor intracellular bacterial survival and metabolic activity following antibiotic treatment. Notably, a subset of intracellular B. melitensis remained metabolically active and capable of resuming growth after exposure to standard-of-care antibiotics. Bacterial replication resumed upon antibiotic washout, supporting the hypothesis that the intracellular niche may protect Brucella from treatment and contribute to relapse. This PBMC-based model provides a physiologically relevant platform for evaluating antibiotic efficacy and exploring novel treatment strategies, including drug repurposing, to improve brucellosis outcomes. |
| Zemlja: | Portal de Revistas UNA |
| Institucija: | Universidad Nacional de Costa Rica |
| Repositorio: | Portal de Revistas UNA |
| Jezik: | Inglés |
| OAI Identifier: | oai:www.revistas.una.ac.cr:article/22846 |
| Online pristup: | https://www.revistas.una.ac.cr/index.php/veterinaria/article/view/22846 |
| Ključna riječ: | Brucella melitensis human brucellosis peripheral blood mononuclear cells |