English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Intracellular pathogens including  Mycobacterium tuberculosis  ( Mtb ) have evolved with strategies to uptake amino acids from host cells to fulfil their metabolic requirements. However,  Mtb  also possesses de novo biosynthesis pathways for all the amino acids. This raises a pertinent question- how does  Mtb  meet its histidine requirements within an in vivo infection setting? Here, we present a mechanism in which the host, by up-regulating its histidine catabolizing enzymes through interferon gamma (IFN-γ) mediated signalling, exerts an immune response directed at starving the bacillus of intracellular free histidine. However, the wild-type  Mtb  evades this host immune response by biosynthesizing histidine de novo, whereas a histidine auxotroph fails to multiply. Notably, in an IFN-γ −/−  mouse model, the auxotroph exhibits a similar extent of virulence as that of the wild-type. The results augment the current understanding of host- Mtb  interactions and highlight the essentiality of  Mtb  histidine biosynthesis for its pathogenesis.

De novo histidine biosynthesis protects Mycobacterium tuberculosis from host IFN-γ mediated histidine starvation