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

Paras Jain, David S. Thaler, Mamoudou Maiga, Graham S. Timmins, William R. Bishai, Graham F. Hatfull, Michelle H. Larsen, William R. Jacobs

Research output: Contribution to journalReview article

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)S1142-S1150
JournalJournal of Infectious Diseases
Volume204
Issue numberSUPPL. 4
DOIs
StatePublished - Nov 15 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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