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In Vitro Analysis of Rates and Spectra of Mutations in a Polymorphic Region of the Rv0746 PE_PGRS Gene of Mycobacterium tuberculosis ^,

Edith E. Machowski,^1,* Samantha Barichievy,^1, Burkhard Springer,² Steven I. Durbach,^1, and Valerie Mizrahi^1*

MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, DST/NRF Centre of Excellence for Biomedical TB Research, School of Pathology of the University of the Witwatersrand and the National Health Laboratory Service, Johannesburg, South Africa,¹ Institut für Medizinische Mikrobiologie, Universität Zürich, Gloriastr. 30/32, CH-8006 Zürich, Switzerland²

Received 24 October 2006/ Accepted 5 December 2006

An assay modeled on a known polymorphism in the PE_PGRS9 gene of Mycobacterium tuberculosis was designed to assess the mutability of a sequence containing interspersed PGRS repeats. Application of the assay in Mycobacterium smegmatis revealed sequence plasticity: in addition to recapitulating the mutation on which it was based, other mutations likely mediated by replication slippage between PGRS repeats were detected. However, the mutation rates argued against marked hypermutability of such sequences in mycobacteria.

Published ahead of print on 15 December 2006.

Supplemental material for this article may be found at http://jb.asm.org/.

E.E.M. and S.B. contributed equally to this study.

Present address: School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa.