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

PLoS Pathogens

Amir Liba¹  Padmini Salgame²  Kamlesh Bhatt²  Shuang Song³  Hélène Botella³  Ruojun Wang³  Julien Vaubourgeix³  Xinzheng V. Guo³  Sabine Ehrt³  Omar H. Vandal³  Nichole Goodsmith³  Dirk Schnappinger³ 

[1] Agilent Technologies, Wilmington, Delaware, United States of America;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;Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America

关键词: Mycobacterium tuberculosis;    Macrophages;    Cell cycle;    cell division;    Peptidoglycans;    Cell walls;    Biosynthesis;    Magnesium;    Gene expression;   

DOI  :  10.1371/journal.ppat.1004645

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY