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Journal of Bacteriology, May 2007, p. 3721-3728, Vol. 189, No. 10
0021-9193/07/$08.00+0     doi:10.1128/JB.01740-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Functional Complementation of the Essential Gene fabG1 of Mycobacterium tuberculosis by Mycobacterium smegmatis fabG but Not Escherichia coli fabG{triangledown}

Tanya Parish,1* Gretta Roberts,1,{dagger} Francoise Laval,2 Merrill Schaeffer,3,{ddagger} Mamadou Daffé,2 and Ken Duncan4,§

Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and the London, London E1 2AT, United Kingdom,1 Institut de Pharmacologie et Biologie Structurale (UMR5089), Department of Molecular Mechanisms of Mycobacterial Infections, Centre National de la Recherche Scientifique and Université Paul Sabatier (Toulouse III), 205 Route de Narbonne, F-31077 Toulouse Cedex, France,2 GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426,3 GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom4

Received 13 November 2006/ Accepted 27 February 2007

Mycolic acids are a key component of the mycobacterial cell wall, providing structure and forming a major permeability barrier. In Mycobacterium tuberculosis mycolic acids are synthesized by type I and type II fatty acid synthases. One of the enzymes of the type II system is encoded by fabG1. We demonstrate here that this gene can be deleted from the M. tuberculosis chromosome only when another functional copy is provided elsewhere, showing that under normal culture conditions fabG1 is essential. FabG1 activity can be replaced by the corresponding enzyme from the closely related species Mycobacterium smegmatis but not by the enzyme from Escherichia coli. M. tuberculosis carrying FabG from M. smegmatis showed no phenotypic changes, and both the mycolic acids and cell wall permeability were unchanged. Thus, M. tuberculosis and M. smegmatis enzymes are interchangeable and do not control the lengths and types of mycolic acids synthesized.


* Corresponding author. Mailing address: Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and the London, London E1 2AT, United Kingdom. Phone: 44 20 7882 2306. Fax: 44 20 7882 2189. E-mail: t.parish{at}qmul.ac.uk

{triangledown} Published ahead of print on 2 March 2007.

{dagger} Present address: Department of Biosurgery & Surgical Technology, Imperial College London, St. Mary's Hospital, Praed Street, London W2 1NY, United Kingdom.

{ddagger} Present address: Boehringer Ingelheim Vetmedica, Inc., 2621 North Belt Highway, Saint Joseph, MO 64506.

§ Present address: Bill and Melinda Gates Foundation, P.O. Box 23350, Seattle, WA 98102.


Journal of Bacteriology, May 2007, p. 3721-3728, Vol. 189, No. 10
0021-9193/07/$08.00+0     doi:10.1128/JB.01740-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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