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

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The success of Mycobacterium tuberculosis (Mtb) as a human pathogen is due to ability to persist in chronic infection, despite a robust adaptive immune response by the host. The mechanisms by which Mtb achieves this are, however, poorly understood. Here we show that a novel integral membrane protein, Rv0955/PerM, is essential for Mtb persistence during chronic mouse infection. The perM mutant required increased magnesium compared to wild type Mtb for replication and survival in culture and elongated in media with reduced magnesium concentration. Transcriptomic, electron microscopy and live cell imaging approaches provided evidence that PerM is involved in cell division. The survival defects of the perM mutant in reduced magnesium and during chronic mouse infection are consistent with the hypothesis that magnesium deprivation constitutes an IFN-γ dependent host defense strategy. This work also has potential clinical implications, as disruption of PerM renders Mtb susceptible to β-lactam antibiotics, which are commonly used to treat non-mycobacterial infections.

Vyšlo v časopise: Disruption of an Membrane Protein Causes a Magnesium-dependent Cell Division Defect and Failure to Persist in Mice. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004645
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004645

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