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Journal of Clinical Microbiology, May 2007, p. 1483-1490, Vol. 45, No. 5
0095-1137/07/$08.00+0     doi:10.1128/JCM.02191-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Recently Evolved Sublineage of the Mycobacterium tuberculosis Beijing Strain Family Is Associated with an Increased Ability to Spread and Cause Disease{triangledown}

M. Hanekom,1 G. D. van der Spuy,1 E. Streicher,1 S. L. Ndabambi,1 C. R. E. McEvoy,1 M. Kidd,3 N. Beyers,2 T. C. Victor,1 P. D. van Helden,1 and R. M. Warren1*

DST/NRF Centre of Excellence for Biomedical Tuberculosis Research/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences,1 Desmond Tutu Tuberculosis Centre, Department of Paediatrics and Child Health,2 Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa, and Centre for Statistical Consultation, Stellenbosch University, Tygerberg, South Africa3

Received 26 October 2006/ Returned for modification 5 February 2007/ Accepted 6 March 2007

This study aimed to reconstruct the evolutionary history of Beijing strains of Mycobacterium tuberculosis and to test the hypothesis that evolution has influenced the ability of the Beijing strains within the different Beijing sublineages to spread and cause disease. A PCR-based method was used to analyze the genome structure of 40 different loci in 325 Beijing isolates collected from new and retreatment tuberculosis patients from an urban setting and 270 Beijing isolates collected from high-risk tuberculosis patients from a rural setting in the Western Cape, South Africa. The resulting data were subjected to phylogenetic analysis using the neighbor joining algorithm. Phylogenetic reconstructions were highly congruent with the "gold standard" phylogenetic tree based on synonymous single-nucleotide polymorphisms, thereby allowing a prediction of the order in which the evolutionary events had occurred. A total of seven independently evolving Beijing sublineages were identified. Analysis of epidemiological data in relation to the Beijing sublineage suggested an association between recent evolutionary change and frequency of occurrence in an urban population (P < 0.001) as well as in the rural population (P < 0.001). This concept was further supported by an association between more recently evolved Beijing strains and an increased ability to transmit and to cause disease (odds ratio, 5.82; 95% confidence interval, 3.13 to 10.82 [P < 0.001]). An association between Beijing sublineage and demographic and clinical parameters and drug resistance could not be demonstrated. From these data, we suggest that the pathogenic characteristics of Beijing strains are not conserved but rather that strains within individual lineages have evolved unique pathogenic characteristics.

* Corresponding author. Mailing address: DST/NRF Centre of Excellence for Biomedical Tuberculosis Research/MRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa. Phone: 21 938 9073. Fax: 21 938 9476. E-mail: rw1{at}sun.ac.za

{triangledown} Published ahead of print on 14 March 2007.

Journal of Clinical Microbiology, May 2007, p. 1483-1490, Vol. 45, No. 5
0095-1137/07/$08.00+0     doi:10.1128/JCM.02191-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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