Logo do repositório
 
Publicação

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

2022-01-13Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorMedley, Jamie
dc.contributor.authorGoff, Aaron
dc.contributor.authorBettencourt, Paulo J. G.
dc.contributor.authorDare, Madelaine
dc.contributor.authorCole, Liam
dc.contributor.authorCantillon, Daire
dc.contributor.authorWaddell, Simon J.
dc.date.accessioned2022-04-01T10:11:31Z
dc.date.available2022-04-01T10:11:31Z
dc.date.issued2022-01-13
dc.description.abstractNew 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/vaccines10010113pt_PT
dc.identifier.eid85123238790
dc.identifier.issn2076-393X
dc.identifier.pmcPMC8780277
dc.identifier.pmid35062774
dc.identifier.urihttp://hdl.handle.net/10400.14/37224
dc.identifier.wos000746680000001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectBCGpt_PT
dc.subjectHost-pathogen interactionspt_PT
dc.subjectMacrophagept_PT
dc.subjectMycobacteriumpt_PT
dc.subjectRNAseqpt_PT
dc.subjectTranscriptomicspt_PT
dc.subjectTuberculosispt_PT
dc.titleDissecting the Mycobacterium bovis BCG response to macrophage infection to help prioritize targets for anti-tuberculosis drug and vaccine discoverypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue1pt_PT
oaire.citation.titleVaccinespt_PT
oaire.citation.volume10pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura indisponível
Nome:
40631678.pdf
Tamanho:
1.65 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

CIIS - Contribuições em Revistas Científicas / Contribution to Journals