TY - JOUR
T1 - Reporter phage and breath tests
T2 - Emerging phenotypic assays for diagnosing active tuberculosis, antibiotic resistance, and treatment efficacy
AU - Jain, Paras
AU - Thaler, David S.
AU - Maiga, Mamoudou
AU - Timmins, Graham S.
AU - Bishai, William R.
AU - Hatfull, Graham F.
AU - Larsen, Michelle H.
AU - Jacobs, William R.
N1 - Funding Information:
Financial support. The work was supported by the National Institutes of Health (AI26170 and AI59877 to W. R. J.); and Albert Einstein College of Medicine Center for AIDS Research (AIO-51519).
PY - 2011/11/15
Y1 - 2011/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80054735136&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80054735136&partnerID=8YFLogxK
U2 - 10.1093/infdis/jir454
DO - 10.1093/infdis/jir454
M3 - Review article
C2 - 21996696
AN - SCOPUS:80054735136
SN - 0022-1899
VL - 204
SP - S1142-S1150
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - SUPPL. 4
ER -