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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum
PLoS Medicine, Volume 5, No. 4, Article e75, Year 2008
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Description
Background: Tuberculous sputum provides a sample of bacilli that must be eliminated by chemotherapy and that may go on to transmit infection. A preliminary observation that Mycobacterium tuberculosis cells contain triacylglycerol lipid bodies in sputum, but not when growing in vitro, led us to investigate the extent of this phenomenon and its physiological basis. Methods and Findings: Microscopy-positive sputum samples from the UK and The Gambia were investigated for their content of lipid body-positive mycobacteria by combined Nile red and auramine staining. All samples contained a lipid body-positive population varying from 3% to 86% of the acid-fast bacilli present. The recent finding that triacylglycerol synthase is expressed by mycobacteria when they enter in vitro nonreplicating persistence led us to investigate whether this state was also associated with lipid body formation. We found that, when placed in laboratory conditions inducing nonreplicating persistence, two M. tuberculosis strains had lipid body levels comparable to those found in sputum. We investigated these physiological findings further by comparing the M. tuberculosis transcriptome of growing and nonreplicating persistence cultures with that obtained directly from sputum samples. Although sputum has traditionally been thought to contain actively growing tubercle bacilli, our transcript analyses refute the hypothesis that these cells predominate. Rather, they reinforce the results of the lipid body analyses by revealing transcriptional signatures that can be clearly attributed to slowly replicating or nonreplicating mycobacteria. Finally, the lipid body count was highly correlated (R2=0.64, p < 0.03) with time to positivity in diagnostic liquid cultures, thereby establishing a direct link between this cytological feature and the size of a potential nonreplicating population. Conclusion: As nonreplicating tubercle bacilli are tolerant to the cidal action of antibiotics and resistant to multiple stresses, identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis. © 2008 Garton et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2276522/bin/pmed.0050075.sg001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC2276522/bin/pmed.0050075.sg002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC2276522/bin/pmed.0050075.st001.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2276522/bin/pmed.0050075.st002.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2276522/bin/pmed.0050075.st003.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2276522/bin/pmed.0050075.st004.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2276522/bin/pmed.0050075.st005.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC2276522/bin/pmed.0050075.st006.doc
Authors & Co-Authors
Garton, Natalie J.
United Kingdom, Leicester
Leicester Medical School
Waddell, Simon J.
United Kingdom, London
St George’s, University of London
Sherratt, Anna L.
United Kingdom, Leicester
Leicester Medical School
Lee, Su Min
United Kingdom, Leicester
Leicester Medical School
Smith, Rebecca J.
United Kingdom, Leicester
Leicester Medical School
Senner, Claire
United Kingdom, London
St George’s, University of London
Hinds, Jason
United Kingdom, London
St George’s, University of London
Rajakumar, Kumar
United Kingdom, Leicester
Leicester Medical School
United Kingdom, Leicester
University Hospitals of Leicester Nhs Trust
Adegbola, Richard A.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Besra, Gurdyal Singh
United Kingdom, Birmingham
University of Birmingham
Butcher, Philip D.
United Kingdom, London
St George’s, University of London
Barer, Michael R.
United Kingdom, Leicester
Leicester Medical School
United Kingdom, Leicester
University Hospitals of Leicester Nhs Trust
Statistics
Citations: 412
Authors: 12
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pmed.0050075
ISSN:
15491277
e-ISSN:
15491676
Research Areas
Cancer
Study Design
Cross Sectional Study
Study Locations
Gambia