Institut Pasteur

The Johns Hopkins University

Medical Research Council

Assistance Publique

Université Pierre Et Marie Curie (Paris Vi)

Universite De Berne

Universite Paris-vi

Ying Zhang

Douglas B Young

Stewart T Cole

Beate Heym

William R Bishai

Nadine Honore

James DeMaio

Amalio Telenti

Thomas Bodmer

Angelo Scorpio

A nucleotide sequence encoding a katG/lacZ fusion protein is useful for assaying the enzymatic activity of the katG gene product. A process of selecting a compound that is toxic against an isoniazid-resistant mycobaterial strain comprises incubating a catalase peroxidase enzyme with an isoniazid to produce a compound that restores isoniazid susceptability to the isoniazid-resistant mycobaterial strain.

Rapid detection of antibiotic resistance in mycobacterium tuberculosis

sigF is a gene that controls M. tuberculosis latency. A diagnostic test for latent tuberculosis involves detecting M. tuberculosis sigF in clinical specimens. Two genes orfX and orfY regulate sigF expression and sigF activity. M. tuberculosis sigF, orfX, and orfY are used in screening methods for potential therapeutic agents which regulate the growth of M. tuberculosis.

Method of identifying compounds that regulate the binding of M.

Multi-drug resistant strains of Mycobacterium tuberculosis represent a considerable threat to public health worldwide. Resistance to isoniazid (INH), a key component of anti-tuberculosis regimens, is often associated with loss of catalase activity and virulence. The katG gene, encoding HPI catalase-peroxidase, mediates INH-sensitivity and that the high level resistance encountered clinically may be due to deletions, insertions or point mutations which reduce or eliminate the expression of the catalase gene in the chromosomal region encompassing katG. INH-resistant strains of Mycobacterium tuberculosis are detected by nucleic acid hybridization with a unique nucleic acid sequence or by amplification techniques.

Nucleic acid probes, sequences and methods for detecting mycobacterium

Disclosed are methods, probes, primers and kits for identifying pyrazinamide-resistant mycobacteria. These methods can be used to distinguish M. bovis from M. tuberculosis, as well as to identify additional pyrazinamide-resistant mycobacteria. Also disclosed are methods for treating mycobacterial infections by expressing a pncA gene in mycobacteria that infect a mammal, and treating the mammal with pyrazinamide. The invention derives from the discovery of that the molecular basis for pyrazinamide resistance is an alteration in the pncA gene of mycobacteria. The detection of such an alteration is an indicator of PZA-resistant mycobacteria.

Identification of pyrazinamide-resistant mycobacteria and methods for

SigF is a gene that controls M. tuberculosis latency. A diagnostic test for latent tuberculosis involves detecting M. tuberculosis sigF in clinical specimens. A tuberculosis vaccine includes a M. tuberculosis strain with a mutation which disrupts the reading frame of its sigF gene.

DNA encoding stationary phase, stress response sigma factor from

Rapid detection of isoniazid resistance in mycobacterium tuberculosis

Growing community of inventors

Baltimore, MD, United States of America

Ying Zhang