Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix

Research output: Contribution to journalArticle


  • Joanna Bacon
  • Jon A Allnutt
  • Evelina Gabasova
  • Robert Watson
  • Kim A Hatch
  • Simon O Clark
  • Rose E Jeeves
  • Alice Marriott
  • Emma Rayner
  • Howard Tolley
  • Geoff Pearson
  • Graham Hall
  • Lorenz Wernisch
  • Ann Williams
  • Philip D Marsh

Colleges, School and Institutes

External organisations

  • Public Health England, Microbiology Services, Porton Down, Salisbury, Wiltshire, United Kingdom.
  • MRC Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom.


A key feature of Mycobacterium tuberculosis is its ability to become dormant in the host. Little is known of the mechanisms by which these bacilli are able to persist in this state. Therefore, the focus of this study was to emulate environmental conditions encountered by M. tuberculosis in the granuloma, and determine the effect of such conditions on the physiology and infectivity of the organism. Non-replicating persistent (NRP) M. tuberculosis was established by the gradual depletion of nutrients in an oxygen-replete and controlled environment. In contrast to rapidly dividing bacilli, NRP bacteria exhibited a distinct phenotype by accumulating an extracellular matrix rich in free mycolate and lipoglycans, with increased arabinosylation. Microarray studies demonstrated a substantial down-regulation of genes involved in energy metabolism in NRP bacteria. Despite this reduction in metabolic activity, cells were still able to infect guinea pigs, but with a delay in the development of disease when compared to exponential phase bacilli. Using these approaches to investigate the interplay between the changing environment of the host and altered physiology of NRP bacteria, this study sheds new light on the conditions that are pertinent to M. tuberculosis dormancy and how this organism could be establishing latent disease.


Original languageEnglish
Article numbere87329
JournalPLoS ONE
Issue number2
Publication statusPublished - 6 Feb 2014


  • Bacterial pathogens, Cell walls, Fatty acids, Gene expression, Granulomas, Lipid analysis, Mycobacterium tuberculosis, Starvation