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Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis

Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis
Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis
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
1552-4450
228-235
Backus, Keriann M.
ad3902be-31eb-4677-b42f-7002e041ccc2
Boshoff, Helena I.
26b1bac8-cdcb-4548-be4d-8a31a4650c73
Barry, Conor S.
60bdcf03-aaec-4872-b938-d2d81fa80c78
Boutureira, Omar
f8a85f70-3513-4c45-885f-26ce364c6093
Patel, Mitul K.
687cfdcc-16c1-41bb-98c2-74bd66a7c8ac
D'Hooge, François
bae35d3d-dd97-41bd-a588-e6c61ce47f96
Lee, Seung Seo
ee34fa26-5fb6-48c8-80c2-1f13ec4ccceb
Via, Laura E.
11313085-c964-4fae-8b16-813be146dc34
Tahlan, Kapil
11b8043d-0be9-4040-82a2-326436fe446d
Barry, Clifton E.
dbf26afe-8ba5-4c03-be83-b4035cb2c38d
Davis, Benjamin G.
2a8a594f-5d71-455a-bd99-d1366c1028cc
Backus, Keriann M.
ad3902be-31eb-4677-b42f-7002e041ccc2
Boshoff, Helena I.
26b1bac8-cdcb-4548-be4d-8a31a4650c73
Barry, Conor S.
60bdcf03-aaec-4872-b938-d2d81fa80c78
Boutureira, Omar
f8a85f70-3513-4c45-885f-26ce364c6093
Patel, Mitul K.
687cfdcc-16c1-41bb-98c2-74bd66a7c8ac
D'Hooge, François
bae35d3d-dd97-41bd-a588-e6c61ce47f96
Lee, Seung Seo
ee34fa26-5fb6-48c8-80c2-1f13ec4ccceb
Via, Laura E.
11313085-c964-4fae-8b16-813be146dc34
Tahlan, Kapil
11b8043d-0be9-4040-82a2-326436fe446d
Barry, Clifton E.
dbf26afe-8ba5-4c03-be83-b4035cb2c38d
Davis, Benjamin G.
2a8a594f-5d71-455a-bd99-d1366c1028cc

Backus, Keriann M., Boshoff, Helena I., Barry, Conor S., Boutureira, Omar, Patel, Mitul K., D'Hooge, François, Lee, Seung Seo, Via, Laura E., Tahlan, Kapil, Barry, Clifton E. and Davis, Benjamin G. (2011) Uptake of unnatural trehalose analogs as a reporter for Mycobacterium tuberculosis. Nature Chemical Biology, 7 (4), 228-235. (PMID:21378984)

Record type: Article

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

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e-pub ahead of print date: 6 March 2011
Published date: April 2011
Organisations: Chemistry

Identifiers

Local EPrints ID: 340225
URI: https://eprints.soton.ac.uk/id/eprint/340225
ISSN: 1552-4450
PURE UUID: fa0f8afb-d76f-41d8-a610-03eb1eb03d60
ORCID for Seung Seo Lee: ORCID iD orcid.org/0000-0002-8598-3303

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Date deposited: 21 Sep 2012 12:28
Last modified: 06 Jun 2018 12:25

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Contributors

Author: Keriann M. Backus
Author: Helena I. Boshoff
Author: Conor S. Barry
Author: Omar Boutureira
Author: Mitul K. Patel
Author: François D'Hooge
Author: Seung Seo Lee ORCID iD
Author: Laura E. Via
Author: Kapil Tahlan
Author: Clifton E. Barry
Author: Benjamin G. Davis

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