Persistent Mycobacterium tuberculosis infection in mice requires PerM for successful cell division

Elife. 2019 Nov 21:8:e49570. doi: 10.7554/eLife.49570.


The ability of Mycobacterium tuberculosis (Mtb) to persist in its host is central to the pathogenesis of tuberculosis, yet the underlying mechanisms remain incompletely defined. PerM, an integral membrane protein, is required for persistence of Mtb in mice. Here, we show that perM deletion caused a cell division defect specifically during the chronic phase of mouse infection, but did not affect Mtb's cell replication during acute infection. We further demonstrate that PerM is required for cell division in chronically infected mice and in vitro under host-relevant stresses because it is part of the mycobacterial divisome and stabilizes the essential divisome protein FtsB. These data highlight the importance of sustained cell division for Mtb persistence, define condition-specific requirements for cell division and reveal that survival of Mtb during chronic infection depends on a persistence divisome.

Keywords: Mycobacterium tuberculosis; cell division; chronic infection; infectious disease; microbiology; persistence.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Cycle Proteins / metabolism
  • Cell Division / physiology*
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Bacterial
  • Gene Knockout Techniques
  • Lung / microbiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / cytology
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / growth & development*
  • Mycobacterium tuberculosis / metabolism*
  • Phenotype
  • Tuberculosis / microbiology


  • Bacterial Proteins
  • Cell Cycle Proteins
  • Membrane Proteins