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Journal of Clinical Microbiology, August 2004, p. 3594-3599, Vol. 42, No. 8
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.8.3594-3599.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Genomic Analysis Distinguishes Mycobacterium africanum

Serge Mostowy,1 Anthony Onipede,2 Sebastien Gagneux,2 Stefan Niemann,3 Kristin Kremer,4 Edward P. Desmond,5 Midori Kato-Maeda,2 and Marcel Behr1*

McGill University Health Centre, Montreal, Canada H3G 1A4,1 Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, California 94305,2 Forschungszentrum Borstel, National Reference Center for Mycobacteria, D-23845 Borstel, Germany,3 Mycobacteria Reference Department, Diagnostic Laboratory for Infectious Diseases and Perinatal Screening, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands,4 Mycobacteriology and Mycology Section, Microbial Diseases Laboratory, California Department of Health Services, Richmond, California 948045

Received 22 March 2004/ Returned for modification 28 April 2004/ Accepted 7 May 2004

Mycobacterium africanum is thought to comprise a unique species within the Mycobacterium tuberculosis complex. M. africanum has traditionally been identified by phenotypic criteria, occupying an intermediate position between M. tuberculosis and M. bovis according to biochemical characteristics. Although M. africanum isolates present near-identical sequence homology to other species of the M. tuberculosis complex, several studies have uncovered large genomic regions variably deleted from certain M. africanum isolates. To further investigate the genomic characteristics of organisms characterized as M. africanum, the DNA content of 12 isolates was interrogated by using Affymetrix GeneChip. Analysis revealed genomic regions of M. tuberculosis deleted from all isolates of putative diagnostic and biological consequence. The distribution of deleted sequences suggests that M. africanum subtype II isolates are situated among strains of "modern" M. tuberculosis. In contrast, other M. africanum isolates (subtype I) constitute two distinct evolutionary branches within the M. tuberculosis complex. To test for an association between deleted sequences and biochemical attributes used for speciation, a phenotypically diverse panel of "M. africanum-like" isolates from Guinea-Bissau was tested for these deletions. These isolates clustered together within one of the M. africanum subtype I branches, irrespective of phenotype. These results indicate that convergent biochemical profiles can be independently obtained for M. tuberculosis complex members, challenging the traditional approach to M. tuberculosis complex speciation. Furthermore, the genomic results suggest a rational framework for defining M. africanum and provide tools to accurately assess its prevalence in clinical specimens.

* Corresponding author. Mailing address: Division of Infectious Diseases and Medical Microbiology, A5-156, Montreal General Hospital, 1650 Cedar Ave., Montreal QC H3G 1A4, Canada. Phone: (514) 934-1934 42815. Fax: (514) 934 8423. E-mail: marcel.behr{at}mcgill.ca.

Journal of Clinical Microbiology, August 2004, p. 3594-3599, Vol. 42, No. 8
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.8.3594-3599.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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