Sulfatase-activated fluorophores for rapid discrimination of mycobacterial species and strains

Kimberly E. Beatty; Monique Williams; Brian L. Carlson; Benjamin M. Swarts; Robin M. Warren; Paul D. Van Helden; Carolyn R. Bertozzi

doi:10.1073/pnas.1222041110

Sulfatase-activated fluorophores for rapid discrimination of mycobacterial species and strains

Kimberly E. Beatty, Monique Williams, Brian L. Carlson, Benjamin M. Swarts, Robin M. Warren, Paul D. Van Helden, Carolyn R. Bertozzi

Chemical Physiology and Biochemistry

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

Most current diagnostic tests for tuberculosis do not reveal the species or strain of pathogen causing pulmonary infection, which can lead to inappropriate treatment regimens and the spread of disease. Here, we report an assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases. We developed a sulfatase-activated probe, 7-hydroxy-9H-(1,3- dichloro-9,9-dimethylacridin-2-one)-sulfate, that detects enzyme activity in native protein gels, allowing the rapid detection of sulfatases in mycobacterial lysates. This assay revealed that mycobacterial strains have distinct sulfatase fingerprints that can be used to judge both the species and lineage. Our results demonstrate the potential of enzyme-activated probes for rapid pathogen discrimination for infectious diseases.

Original language	English (US)
Pages (from-to)	12911-12916
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	110
Issue number	32
DOIs	https://doi.org/10.1073/pnas.1222041110
State	Published - Aug 6 2013

Keywords

Chemical biology
Enzyme assay
Fluorescence
Hydrolase
Mycobacterium tuberculosis

ASJC Scopus subject areas

General

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10.1073/pnas.1222041110

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title = "Sulfatase-activated fluorophores for rapid discrimination of mycobacterial species and strains",

abstract = "Most current diagnostic tests for tuberculosis do not reveal the species or strain of pathogen causing pulmonary infection, which can lead to inappropriate treatment regimens and the spread of disease. Here, we report an assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases. We developed a sulfatase-activated probe, 7-hydroxy-9H-(1,3- dichloro-9,9-dimethylacridin-2-one)-sulfate, that detects enzyme activity in native protein gels, allowing the rapid detection of sulfatases in mycobacterial lysates. This assay revealed that mycobacterial strains have distinct sulfatase fingerprints that can be used to judge both the species and lineage. Our results demonstrate the potential of enzyme-activated probes for rapid pathogen discrimination for infectious diseases.",

keywords = "Chemical biology, Enzyme assay, Fluorescence, Hydrolase, Mycobacterium tuberculosis",

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AU - Beatty, Kimberly E.

AU - Williams, Monique

AU - Carlson, Brian L.

AU - Swarts, Benjamin M.

AU - Warren, Robin M.

AU - Van Helden, Paul D.

AU - Bertozzi, Carolyn R.

PY - 2013/8/6

Y1 - 2013/8/6

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AB - Most current diagnostic tests for tuberculosis do not reveal the species or strain of pathogen causing pulmonary infection, which can lead to inappropriate treatment regimens and the spread of disease. Here, we report an assay for mycobacterial strain assignment based on genetically conserved mycobacterial sulfatases. We developed a sulfatase-activated probe, 7-hydroxy-9H-(1,3- dichloro-9,9-dimethylacridin-2-one)-sulfate, that detects enzyme activity in native protein gels, allowing the rapid detection of sulfatases in mycobacterial lysates. This assay revealed that mycobacterial strains have distinct sulfatase fingerprints that can be used to judge both the species and lineage. Our results demonstrate the potential of enzyme-activated probes for rapid pathogen discrimination for infectious diseases.

KW - Chemical biology

KW - Enzyme assay

KW - Fluorescence

KW - Hydrolase

KW - Mycobacterium tuberculosis

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Sulfatase-activated fluorophores for rapid discrimination of mycobacterial species and strains

Abstract

Keywords

ASJC Scopus subject areas

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