Intracellular heterogeneity contributes to antibiotic treatment survival
Sparad:
| Författarna: | , , , |
|---|---|
| Materialtyp: | artículo original |
| Status: | Versión publicada |
| Utgivningstid: | 2026 |
| Beskrivning: | Canine human brucellosis requires prolonged treatment with a combination of antibiotics. Despite this intensive regimen, relapse rates remain high. We have previously demon- strated that a small subpopulation of phagocytosed Brucella abortus can survive antibiotic treatment and retain full virulence in a macrophage infection model, potentially serving as a reservoir for relapses. To better characterize this surviving subpopulation, we devel- oped a BSL2-compatible infection model based on Brucella microti, which recapitulates the previously observed “persister” phenotype— displaying biphasic killing in broth and intracellular survival after antibiotic treatment. Using B. microti as a proxy, we show that phagocytosed bacteria retained in the endocytic network survive antibiotic exposure dis- playing high antibiotic tolerance. Notably, the stage of intracellular trafficking at treatment initiation does not affect survival rates, indicating the existence of tolerant bacteria before treatment start. Building on these findings, we are developing a high-throughput screening platform to identify drugs capable of targeting this persistent intracellular subpopulation. Given that only a subset of wild-type bacteria transition to the replication-permissive, ER- associated niche—while the majority remains in a growth-arrested state—we hypothesize that this physiological heterogeneity represents a classical bet-hedging strategy employed by Brucella to ensure survival in adverse conditions and a better understanding of this strategy can help adopting more efficacious treatment schemes. |
| Land: | Portal de Revistas UNA |
| Organisation: | Universidad Nacional de Costa Rica |
| Repositorio: | Portal de Revistas UNA |
| Språk: | Inglés |
| OAI Identifier: | oai:www.revistas.una.ac.cr:article/22842 |
| Länkar: | https://www.revistas.una.ac.cr/index.php/veterinaria/article/view/22842 |
| Nyckelord: | Brucella microti Brucella abortus antibiotic tolerance |