Disruption of an M. tuberculosis Membrane Protein Causes a Magnesium-dependent Cell Division Defect and Failure to Persist in Mice

Nichole Goodsmith, Xinzheng V. Guo, Omar H. Vandal, Julien Vaubourgeix, Ruojun Wang, Hélène Botella, Shuang Song, Kamlesh Bhatt, Amir Liba, Padmini Salgame, Dirk Schnappinger, Sabine Ehrt

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The identification of Mycobacterium tuberculosis genes necessary for persistence in vivo provides insight into bacterial biology as well as host defense strategies. We show that disruption of M. tuberculosis membrane protein PerM (Rv0955) resulted in an IFN-γ-dependent persistence defect in chronic mouse infection despite the mutant’s near normal growth during acute infection. The perM mutant required increased magnesium for replication and survival; incubation in low magnesium media resulted in cell elongation and lysis. Transcriptome analysis of the perM mutant grown in reduced magnesium revealed upregulation of cell division and cell wall biosynthesis genes, and live cell imaging showed PerM accumulation at the division septa in M. smegmatis. The mutant was acutely sensitive to β-lactam antibiotics, including specific inhibitors of cell division-associated peptidoglycan transpeptidase FtsI. Together, these data implicate PerM as a novel player in mycobacterial cell division and pathogenesis, and are consistent with the hypothesis that immune activation deprives M. tuberculosis of magnesium.

Original languageEnglish (US)
Article numbere1004645
JournalPLoS pathogens
Volume11
Issue number2
DOIs
StatePublished - Jan 1 2015

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Goodsmith, N., Guo, X. V., Vandal, O. H., Vaubourgeix, J., Wang, R., Botella, H., Song, S., Bhatt, K., Liba, A., Salgame, P., Schnappinger, D., & Ehrt, S. (2015). Disruption of an M. tuberculosis Membrane Protein Causes a Magnesium-dependent Cell Division Defect and Failure to Persist in Mice. PLoS pathogens, 11(2), [e1004645]. https://doi.org/10.1371/journal.ppat.1004645