Rapid assessment of drug susceptibilities of mycobacterium tuberculosis by means of luciferase reporter phages

William R. Jacobs, Raúl G. Barletta, Rupa Udani, John Chan, Gary Kalkut, Gabriel Sosne, Tobias Kieser, Gary J. Sarkis, Graham F. Hatfull, Barry R. Bloom

Research output: Contribution to journalArticlepeer-review

359 Scopus citations

Abstract

Effective chemotherapy of tuberculosis requires rapid assessment of drug sensitivity because of the emergence of multidrug-resistant Mycobacterium tuberculosis. Drug susceptibility was assessed by a simple method based on the efficient production of photons by viable mycobacteria infected with specific reporter phages expressing the firefly luciferase gene. Light production was dependent on phage infection, expression of the luciferase gene, and the level of cellular adenosine triphospnate. Signals could be detected within minutes after infection of virulent M. tuberculosis with reporter phages. Culture of conventional strains with antituberculosis drugs, including isoniazid or rifampicin, resulted in extinction of light production. In contrast, light signals after luciferase reporter phage infection of drug-resistant strains continued to be produced. Luciferase reporter phages may help to reduce the time required for establishing antibiotic sensitivity of M. tuberculosis strains from weeks to days and to accelerate screening for new antituberculosis drugs.

Original languageEnglish (US)
Pages (from-to)819-822
Number of pages4
JournalScience
Volume260
Issue number5109
StatePublished - 1993

ASJC Scopus subject areas

  • General

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