For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

Disruption of an M. tuberculosis membrane protein causes a magnesium-dependent cell division defect and failure to persist in mice.

TitleDisruption of an M. tuberculosis membrane protein causes a magnesium-dependent cell division defect and failure to persist in mice.
Publication TypeJournal Article
Year of Publication2015
AuthorsGoodsmith N, Guo XV, Vandal OH, Vaubourgeix J, Wang R, Botella H, Song S, Bhatt K, Liba A, Salgame P, Schnappinger D, Ehrt S
JournalPLoS Pathog
Volume11
Issue2
Paginatione1004645
Date Published2015 Feb
ISSN1553-7374
KeywordsAnimals, Bacterial Proteins, Cell Division, Disease Models, Animal, Female, Magnesium, Membrane Proteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium tuberculosis, Tuberculosis
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.

DOI10.1371/journal.ppat.1004645
Alternate JournalPLoS Pathog
PubMed ID25658098
PubMed Central IDPMC4450064
Grant ListT32 GM007739 / GM / NIGMS NIH HHS / United States
U19 AI107774 / AI / NIAID NIH HHS / United States
R01 AI081725 / AI / NIAID NIH HHS / United States
T32GM07739 / GM / NIGMS NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587