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Journal of Clinical Microbiology, April 1999, p. 971-975, Vol. 37, No. 4
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Molecular Markers Demonstrate that the First Described Multidrug-Resistant Mycobacterium bovis Outbreak Was Due to Mycobacterium tuberculosis

M. C. Gutiérrez,1 J. C. Galán,2 J. Blázquez,2 E. Bouvet,3 and V. Vincent1,*

Centre National de Référence des Mycobactéries, Institut Pasteur,1 and Clinique de Réanimation des Maladies Infectieuses, Hôpital Bichat-Claude Bernard,3 Paris, France, and Servicio de Microbiología, Hospital Ramón y Cajal, Madrid, Spain2

Received 14 October 1998/Returned for modification 19 November 1998/Accepted 7 January 1998

We genetically characterized multidrug-resistant Mycobacterium tuberculosis complex strains which caused a nosocomial outbreak of tuberculosis affecting six human immunodeficiency virus (HIV)-positive patients and one HIV-negative staff member (E. Bouvet, E. Casalino, G. Mendoza-Sassi, S. Lariven, E. Vallée, M. Pernet, S. Gottot, and F. Vachon, AIDS 7:1453-1460, 1993). The strains showed all the phenotypic characteristics of Mycobacterium bovis. They presented a high copy number of IS6110, the spacers 40 to 43 in the direct repeat locus, and the mtp40 fragment. They lacked the G-A mutation at position 285 in the oxyR gene and the C-G mutation at position 169 in the pncA gene. These genetic characteristics revealed that these were dysgonic, slow-growing M. tuberculosis strains mimicking the M. bovis phenotype, probably as a consequence of cellular alterations associated with the multidrug resistance. Spoligotyping and IS6110 restriction fragment length polymorphism (RFLP) analysis confirmed that the outbreak was due to a single strain. However, the IS6110 RFLP pattern of the strain isolated from the last patient, diagnosed three years after the index case, differed slightly from the patterns of the other six strains. A model of a possible genetic event is presented to explain this divergence. This study stresses the value of using several independent molecular markers to identify multidrug-resistant tubercle bacilli.

* Corresponding author. Mailing address: Centre National de Référence des Mycobactéries, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: (33) (1) 45688360. Fax: (33) (1) 40613118. E-mail: vvincent{at}pasteur.fr.

Journal of Clinical Microbiology, April 1999, p. 971-975, Vol. 37, No. 4
0095-1137/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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