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

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 granu...

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Bibliographic Details
Published in:PloS one 2014-02, Vol.9 (2), p.e87329
Main Authors: Bacon, Joanna, Alderwick, Luke J, Allnutt, Jon A, Gabasova, Evelina, Watson, Robert, Hatch, Kim A, Clark, Simon O, Jeeves, Rose E, Marriott, Alice, Rayner, Emma, Tolley, Howard, Pearson, Geoff, Hall, Graham, Besra, Gurdyal S, Wernisch, Lorenz, Williams, Ann, Marsh, Philip D
Format: Article
Language:English
Subjects:
Adaptation
Adaptation, Physiological - drug effects
Adaptation, Physiological - genetics
Animals
Bacilli
Bacteria
Bacterial Load - drug effects
Bacterial Load - genetics
Besra
Biology
Carbohydrates
Carbohydrates - chemistry
Carbon
Carbon - pharmacology
Cell Wall - drug effects
Cell Wall - metabolism
Cell walls
Chemistry
Chromatography, Thin Layer
Development and progression
Dormancy
Electrophoresis, Polyacrylamide Gel
Energy metabolism
Environmental conditions
Extracellular matrix
Extracellular Matrix - drug effects
Extracellular Matrix - metabolism
Fatty acids
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Bacterial - drug effects
Gene regulation
Granuloma
Growth models
Guinea Pigs
Hypoxia
Infections
Infectivity
Kinases
Lipids
Mathematics
Medicine
Metabolism
Mice
Molecular Sequence Annotation
Multigene Family
Mycobacterium Infections - genetics
Mycobacterium Infections - microbiology
Mycobacterium Infections - pathology
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - growth & development
Mycobacterium tuberculosis - pathogenicity
Mycobacterium tuberculosis - ultrastructure
Nutrients
Oxygen
Physiological aspects
Physiology
Polysorbates - pharmacology
Proteins
Public health
Replicating
Replication
Studies
Tuberculosis
Up-Regulation - genetics
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0087329