Host glyceraldehyde-3-phosphate dehydrogenase-mediated iron acquisition is hijacked by intraphagosomal Mycobacterium tuberculosis

Anil Patidar, Himanshu Malhotra, Surbhi Chaudhary, Manoj Kumar, Rahul Dilawari, Gaurav Kumar Chaubey, Asmita Dhiman, Radheshyam Modanwal, Sharmila Talukdar, Chaaya Iyengar Raje, Manoj Raje

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Availability of iron is a key factor in the survival and multiplication of Mycobacterium tuberculosis (M.tb) within host macrophage phagosomes. Despite host cell iron regulatory machineries attempts to deny supply of this essential micronutrient, intraphagosomal M.tb continues to access extracellular iron. In the current study, we report that intracellular M.tb exploits mammalian secreted Glyceraldehyde 3-phosphate dehydrogenase (sGAPDH) for the delivery of host iron carrier proteins lactoferrin (Lf) and transferrin (Tf). Studying the trafficking of iron carriers in infected cells we observed that sGAPDH along with the iron carrier proteins are preferentially internalized into infected cells and trafficked to M.tb containing phagosomes where they are internalized by resident mycobacteria resulting in iron delivery. Collectively our findings provide a new mechanism of iron acquisition by M.tb involving the hijack of host sGAPDH. This may contribute to its successful pathogenesis and provide an option for targeted therapeutic intervention.

Original languageEnglish (US)
Article number62
JournalCellular and Molecular Life Sciences
Volume79
Issue number1
DOIs
StatePublished - Jan 2022
Externally publishedYes

Keywords

  • GAPDH
  • Iron
  • Lactoferrin
  • Lipoarabinomannan (LAM)
  • M.tb
  • Targeted delivery
  • Transferrin

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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