Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid

Catherine Vilchèze; Feng Wang; Masayoshi Arai; Manzour Hernando Hazbón; Roberto Colangeli; Laurent Kremer; Torin R Weisbrod; David Alland; James C Sacchettini; William R Jacobs; Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

doi:10.1038/nm1466

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Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid

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Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid

Catherine Vilchèze, Feng Wang, Masayoshi Arai, Manzour Hernando Hazbón, Roberto Colangeli, Laurent Kremer, Torin R Weisbrod, David Alland, James C Sacchettini, William R Jacobs, …

Nature medicine, Vol.12(9), pp.1027-1029

01/09/2006

DOI: https://doi.org/10.1038/nm1466

PMID: 16906155

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Article

Biomedical and Life Sciences

Biomedicine

brief-communication

Cancer Research

Général

Infectious Diseases

Metabolic Diseases

Molecular Medicine

Neurosciences

Isoniazid is one of the most effective antituberculosis drugs, yet its precise mechanism of action is still controversial. Using specialized linkage transduction, a single point mutation allele (S94A) within the putative target gene inhA was transferred in Mycobacterium tuberculosis . The inhA (S94A) allele was sufficient to confer clinically relevant levels of resistance to isoniazid killing and inhibition of mycolic acid biosynthesis. This resistance correlated with the decreased binding of the INH-NAD inhibitor to InhA, as shown by enzymatic and X-ray crystallographic analyses, and establishes InhA as the primary target of isoniazid action in M. tuberculosis .

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Titre: Transfer of a point mutation in Mycobacterium tuberculosis inhA resolves the target of isoniazid
Créateurs - sans rôle: Catherine Vilchèze - Albert Einstein College of Medicine
Feng Wang - Department of Biochemistry and Biophysics, Texas A&M University, College Station
Masayoshi Arai - Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine
Manzour Hernando Hazbón - Division of Infectious Disease, Department of Medicine and the Ruy V. Lourenço Center for the Study of Emerging and Re-emerging Pathogens, New Jersey Medical School, University of Medicine and Dentistry of New Jersey
Roberto Colangeli - Division of Infectious Disease, Department of Medicine and the Ruy V. Lourenço Center for the Study of Emerging and Re-emerging Pathogens, New Jersey Medical School, University of Medicine and Dentistry of New Jersey
Laurent Kremer - Université de Montpellier
Torin R Weisbrod - Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine
David Alland - Rutgers New Jersey Medical School
James C Sacchettini - Department of Biochemistry and Biophysics, Texas A&M University, College Station
William R Jacobs - Albert Einstein College of Medicine
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Détails de publication: Nature medicine, Vol.12(9), pp.1027-1029
Éditeur: Nature Publishing Group US
Nombre de pages: 3
Identifiants: 99155437309311
Unité académique: Institut de Recherche en Infectiologie de Montpellier - IRIM
Langue: English
Type de ressource: Journal article