Polyphosphate kinase-1 regulates bacterial and host metabolic pathways involved in pathogenesis of Mycobacterium tuberculosis

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Chugh, Saurabh | Tiwari, Prabhakar | Suri, Charu | Gupta, Sonu, Kumar | Singh, Padam | Bouzeyen, Rania | Kidwai, Saqib | Srivastava, Mitul | Rameshwaram, Nagender, Rao | Kumar, Yashwant | Asthana, Shailendra | Singh, Ramandeep

Edité par CCSD ; National Academy of Sciences -

International audience. SignificanceInorganic polyphosphate (polyP), a linear polymer of hundreds of phosphate residues, is synthesized by Polyphosphate kinase-1 (PPK-1). Studies have shown that polyP dysregulation impairs Mycobacterium tuberculosis growth in host tissues. Overall, our work provides a detailed mechanistic perspective on regulation of mycobacterial pathogenesis by deletion of ppk-1. We show that deletion of ppk-1 affects glucose utilization and lipid biosynthesis in M. tuberculosis. In addition, the lungs of Δppk-1 mutant strain-infected mice had reduced transcript levels of genes encoding for proteins involved in antimicrobial pathways. We have also identified a broad-spectrum inhibitor against the PPK-1 enzyme. We anticipate that PPK-1 targeting small molecules can reduce the duration of chemotherapy and be effective against bacteria that require polyP for virulence.

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