title: Disruption of an M. tuberculosis membrane protein causes a magnesium-dependent cell division defect and failure to persist in mice.
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.
authors: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors: Nichole
authors: N
authors: Goodsmith
authors: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors: Xinzheng V
authors: XV
authors: Guo
authors: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors: Omar H
authors: OH
authors: Vandal
authors: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors: Julien
authors: J
authors: Vaubourgeix
authors: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors: Ruojun
authors: R
authors: Wang
authors: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors: Hélène
authors: H
authors: Botella
authors: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors: Shuang
authors: S
authors: Song
authors: Department of Medicine, Center for Emerging Pathogens, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, United States of America.
authors: Kamlesh
authors: K
authors: Bhatt
authors: Agilent Technologies, Wilmington, Delaware, United States of America.
authors: Amir
authors: A
authors: Liba
authors: Department of Medicine, Center for Emerging Pathogens, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, United States of America.
authors: Padmini
authors: P
authors: Salgame
authors: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors: Dirk
authors: D
authors: Schnappinger
authors: Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America.
authors: Sabine
authors: S
authors: Ehrt
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D008274:Magnesium / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000378:metabolism*; D014376:Tuberculosis / Q000276:immunology / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D008274:Magnesium