ADP-ribosylation-resistant rifabutin analogs show improved bactericidal activity against drug-tolerant M. abscessus in caseum surrogate

Necrotic lesions and cavities filled with caseum are a hallmark of mycobacterial pulmonary disease. Bronchocavitary Mycobacterium abscessus disease is associated with poor treatment outcomes. In caseum surrogate, M. abscessus entered an extended stationary phase showing tolerance to killing by most...

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Detalles Bibliográficos
Autores principales: Xie, Min, Ganapathy, Uday S., Lan, Tian, Osiecki, Paulina, Sarathy, Jansy P., Dartois, Véronique, Aldrich, Courtney C., Dick, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Experimental Therapeutics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508146/
https://www.ncbi.nlm.nih.gov/pubmed/37493373
http://dx.doi.org/10.1128/aac.00381-23
Descripción
Sumario:Necrotic lesions and cavities filled with caseum are a hallmark of mycobacterial pulmonary disease. Bronchocavitary Mycobacterium abscessus disease is associated with poor treatment outcomes. In caseum surrogate, M. abscessus entered an extended stationary phase showing tolerance to killing by most current antibiotics, suggesting that caseum persisters contribute to the poor performance of available treatments. Novel ADP-ribosylation-resistant rifabutin analogs exhibited bactericidal activity against these M. abscessus persisters at concentrations achievable by rifamycins in caseum.

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