Dissecting the Mycobacterium bovis BCG response to macrophage infection to help prioritize targets for anti-tuberculosis drug and vaccine discovery

Jamie Medley, Aaron Goff, Paulo J. G. Bettencourt, Madelaine Dare, Liam Cole, Daire Cantillon, Simon J. Waddell*

*Autor correspondente para este trabalho

Resultado de pesquisarevisão de pares

3 Citações (Scopus)
2 Transferências (Pure)

Resumo

New strategies are required to reduce the worldwide burden of tuberculosis. Intracellular survival and replication of Mycobacterium tuberculosis after macrophage phagocytosis is a fundamental step in the complex host–pathogen interactions that lead to granuloma formation and disease. Greater understanding of how the bacterium survives and thrives in these environments will inform novel drug and vaccine discovery programs. Here, we use in-depth RNA sequencing of Mycobacterium bovis BCG from human THP-1 macrophages to describe the mycobacterial adaptations to the intracellular environment. We identify 329 significantly differentially regulated genes, highlighting cholesterol catabolism, the methylcitrate cycle and iron homeostasis as important for mycobacteria inside macrophages. Examination of multi-functional gene families revealed that 35 PE/PPE genes and five cytochrome P450 genes were upregulated 24 h after infection, highlighting pathways of potential significance. Comparison of the intracellular transcriptome to gene essentiality and immunogenicity studies identified 15 potential targets that are both required for intracellular survival and induced on infection, and eight upregulated genes that have been demonstrated to be immunogenic in TB patients. Further insight into these new and established targets will support drug and vaccine development efforts.
Idioma originalEnglish
Número do artigo113
Número de páginas14
RevistaVaccines
Volume10
Número de emissão1
DOIs
Estado da publicaçãoPublished - 13 jan 2022

Impressão digital

Mergulhe nos tópicos de investigação de “Dissecting the Mycobacterium bovis BCG response to macrophage infection to help prioritize targets for anti-tuberculosis drug and vaccine discovery“. Em conjunto formam uma impressão digital única.

Citação