Cited by 237Tuberculosis Research and EpidemiologyClick Chemistry and ApplicationsCarbohydrate Chemistry and Synthesis

Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis

Open access
Backus, Keriann M, Boshoff, Helena I, Barry, Conor S, Boutureira, Omar, Patel, Mitul K, D'Hooge, François, Lee, Seung Seo, Via, Laura E +3 more·2011·Nature Chemical Biology

Abstract

The detection of tuberculosis currently relies upon insensitive and unspecific techniques; newer diagnostics would ideally co-opt specific bacterial processes to provide real-time readouts. The trehalose mycolyltransesterase enzymes (antigens 85A, 85B and 85C (Ag85A, Ag85B, Ag85C)) serve as essential mediators of cell envelope function and biogenesis in Mycobacterium tuberculosis. Through the construction of a systematically varied sugar library, we show here that Ag85 enzymes have exceptionally broad substrate specificity. This allowed exogenously added synthetic probes to be specifically incorporated into M. tuberculosis growing in vitro and within macrophages. Even bulky substituents, such as a fluorescein-containing trehalose probe (FITC-trehalose), were incorporated by growing bacilli, thereby producing fluorescent bacteria; microscopy revealed selective labeling of poles and membrane. Addition of FITC-trehalose to M. tuberculosis-infected macrophages allowed selective, sensitive detection of M. tuberculosis within infected mammalian macrophages. These studies suggest that analogs of trehalose may prove useful as probes of function and for other imaging modalities.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nchembio.539

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Bioorthogonal metabolic labeling allows the biosynthesis of trehalose-containing molecules, peptidoglycans, and arabinan to be visualized in situ in both M. smegmatis and M. tuberculosis.

    “Nevertheless, there are emerging efforts to apply modern (click chemistry) approaches of bioorthogonal metabolic labeling in both M. smegmatis and M. tuberculosis, allowing the biosynthesis of trehalose-containing molecules, peptidoglycans, and arabinan to be visualized in situ (116, 163–165).”

    From Mycobacterium smegmatis: The Vanguard of Mycobacterial Research (2023) · cites this paper as [164]

    The Results section ('FITC-trehalose specifically labels M. tuberculosis in vitro'; page unavailable) reports fluorescent visualization of trehalose-probe incorporation in live M. tuberculosis. This paper does not demonstrate the claimed labeling of peptidoglycan or arabinan, or the use of click chemistry; its mention of M. smegmatis is background rather than a demonstration of this probe in that species. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. [48]Anderson DH An interfacial mechanism and a class of inhibitors inferred from two crystal structures of the Mycobacterium tuberculosis 30 kDa major secretory protein (Antigen 85B), a mycolyl transferase J Mol Biol 307 671 681 2001 11254389

Cited by

Sorted by citations

Authors
Backus, K. M., Boshoff, H. I., Barry, C. S., Boutureira, O., Patel, M. K., D'Hooge, F., Lee, S. S., Via, L. E., Tahlan, K., Barry, C. E., & Davis, B. G.
Affiliations
  • University of Oxford (GB)
  • National Institute of Allergy and Infectious Diseases (US)
Corresponding author
  • Barry, Conor S
  • Barry, Clifton E
  • Davis, Benjamin G
Venue
Nature Chemical Biology
Published
2011-03-06
Volume
7
Issue
4
Pages
228-235
ISSN
  • 1552-4450 (ISSN-L)
  • 1552-4469
OpenAlex
W2068962699
Cited by
237
References
46
Citations by year
2026: 8 · 2025: 14 · 2024: 17 · 2023: 18 · 2022: 21 · 2021: 16 · 2020: 23 · 2019: 18 · 2018: 19 · 2017: 15 · 2016: 13 · 2015: 11 · 2014: 15 · 2013: 10 · 2012: 10
FWCI
9.54
Type
journal article
Language
en
Open access
Locations
  • Nature Chemical Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
Funders
  • National Institutes of Health
  • Engineering and Physical Sciences Research Council (EP/E000614/1, EP/D023343/1, GR/T26542/01, EP/I500200/1, EP/G026688/1, EP/D023335/1)
  • Biotechnology and Biological Sciences Research Council (BB/C510824/1, BB/E004350/1, EGA17763)
  • National Institute of Allergy and Infectious Diseases (Z01AI000693, ZIAAI000693, ZIAAI000734)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
  • Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
Keywords
Mycobacterium tuberculosis, substrate specificity, fluorescent probes, bacterial cell wall, macrophage infection, tuberculosis diagnosis, bacterial imaging
MeSH terms
Animals, Cell Line, Fluorescent Dyes, Macrophages, Microscopy, Fluorescence, Mycobacterium tuberculosis, Mass Spectrometry, Substrate Specificity, Trehalose, Genes, Reporter, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review