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Reporter phage and breath tests: Emerging phenotypic assays for diagnosing active tuberculosis, antibiotic resistance, and treatment efficacy

Jain, P and Thaler, DS and Maiga, M and Timmins, GS and Bishai, WR and Hatfull, GF and Larsen, MH and Jacobs, WR (2011) Reporter phage and breath tests: Emerging phenotypic assays for diagnosing active tuberculosis, antibiotic resistance, and treatment efficacy. Journal of Infectious Diseases, 204 (SUPPL.). ISSN 0022-1899

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The rapid and accurate diagnosis of active tuberculosis (TB) and its drug susceptibility remain a challenge. Phenotypic assays allow determination of antibiotic susceptibilities even if sequence data are not available or informative. We review 2 emerging diagnostic approaches, reporter phage and breath tests, both of which assay mycobacterial metabolism. The reporter phage signal, Green fluorescent protein (GFP) or β-galactosidase, indicates transcription and translation inside the recipient bacilli and its attenuation by antibiotics.Different breath tests assay, (1) exhaled antigen 85, (2) mycobacterial urease activity, and (3) detection by trained rats of diseasespecific odor in sputum, have also been developed. When compared with culture, reporter phage assays shorten the time for initial diagnosis of drug susceptibility by several days. Both reporter phage and breath tests have promise as early markers to determine the efficacy of treatment. While sputum often remains smear and Mycobacterium tuberculosis DNA positive early in the course of efficacious antituberculous treatment, we predict that both breath and phage tests will rapidly become negative. If this hypothesis proves correct, phage assays and breath tests could become important surrogate markers in early bactericidal activity (EBA) studies of new antibiotics. © The Author 2011.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Jain, P
Thaler, DS
Maiga, M
Timmins, GS
Bishai, WR
Hatfull, GFgfh@pitt.eduGFH
Larsen, MH
Jacobs, WR
Date: 15 November 2011
Date Type: Publication
Journal or Publication Title: Journal of Infectious Diseases
Volume: 204
Number: SUPPL.
DOI or Unique Handle: 10.1093/infdis/jir454
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Refereed: Yes
ISSN: 0022-1899
Article Type: Review
MeSH Headings: Animals; Antitubercular Agents--pharmacology; Antitubercular Agents--therapeutic use; Breath Tests--methods; Flow Cytometry; Genes, Reporter--genetics; Humans; Microbial Sensitivity Tests--methods; Mycobacteriophages--genetics; Mycobacterium tuberculosis--classification; Mycobacterium tuberculosis--drug effects; Mycobacterium tuberculosis--isolation & purification; Mycobacterium tuberculosis--metabolism; Phenotype; Rats; Tuberculosis--diagnosis; Tuberculosis--drug therapy; Tuberculosis--microbiology
Other ID: NLM PMC3247800 [Available on 11/15/12]
PubMed Central ID: PMC3247800
PubMed ID: 21996696
Date Deposited: 29 Nov 2012 21:00
Last Modified: 03 Jan 2023 12:56


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