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

作者：Goodsmith Nichole^*; Guo Xinzheng V; Vandal Omar H; Vaubourgeix Julien; Wang Ruojun; Botella Helene; Song Shuang; Bhatt Kamlesh; Liba Amir; Salgame Padmini; Schnappinger Dirk; Ehrt Sabine

来源：PLoS Pathogens, 2015, 11(2): e1004645.

DOI：10.1371/journal.ppat.1004645

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-gamma-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 beta-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.

• 出版日期2015-2
• 单位rutgers