Path-seq identifies an essential mycolate remodeling program for mycobacterial host adaptation.
Mol Syst Biol
; 15(3): e8584, 2019 03 04.
Article
em En
| MEDLINE
| ID: mdl-30833303
ABSTRACT
The success of Mycobacterium tuberculosis (MTB) stems from its ability to remain hidden from the immune system within macrophages. Here, we report a new technology (Path-seq) to sequence miniscule amounts of MTB transcripts within up to million-fold excess host RNA Using Path-seq and regulatory network analyses, we have discovered a novel transcriptional program for in vivo mycobacterial cell wall remodeling when the pathogen infects alveolar macrophages in mice. We have discovered that MadR transcriptionally modulates two mycolic acid desaturases desA1/desA2 to initially promote cell wall remodeling upon in vitro macrophage infection and, subsequently, reduces mycolate biosynthesis upon entering dormancy. We demonstrate that disrupting MadR program is lethal to diverse mycobacteria making this evolutionarily conserved regulator a prime antitubercular target for both early and late stages of infection.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Tuberculose
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Redes Reguladoras de Genes
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Interações Hospedeiro-Patógeno
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Macrófagos
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Mycobacterium tuberculosis
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Antígenos de Bactérias
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article