The Salmonella virulence protein MgtC promotes phosphate uptake inside macrophages

Soomin Choi, Eunna Choi, Yong Joon Cho, Daesil Nam, Jangwoo Lee, Eun Jin Lee

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

The MgtC virulence protein from the intracellular pathogen Salmonella enterica is required for its intramacrophage survival and virulence in mice and this requirement of MgtC is conserved in several intracellular pathogens including Mycobacterium tuberculosis. Despite its critical role in survival within macrophages, only a few molecular targets of the MgtC protein have been identified. Here, we report that MgtC targets PhoR histidine kinase and activates phosphate transport independently of the available phosphate concentration. A single amino acid substitution in PhoR prevents its binding to MgtC, thus abrogating MgtC-mediated phosphate transport. Surprisingly, the removal of MgtC’s effect on the ability to transport phosphate renders Salmonella hypervirulent and decreases a non-replicating population inside macrophages, indicating that MgtC-mediated phosphate transport is required for normal Salmonella pathogenesis. This provides an example of a virulence protein directly activating a pathogen’s phosphate transport inside host.

Original languageEnglish
Article number3326
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

Bibliographical note

Funding Information:
We thank Drs. Yunje Cho and Nam-Chul Ha for their thoughtful comments on PhoR structural modeling. This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2019R1A2C2003460) and Korea University grants (K1823071 and K1821661) to E.L., and by a grant in the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2018R1D1A1B07043844) to E.C.

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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