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Infection and Immunity, September 2002, p. 5290-5294, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5290-5294.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

A Mutant of Burkholderia pseudomallei, Auxotrophic in the Branched Chain Amino Acid Biosynthetic Pathway, Is Attenuated and Protective in a Murine Model of Melioidosis

T. Atkins,1* R. G. Prior,1 K. Mack,1 P. Russell,1 M. Nelson,1 P. C. F. Oyston,1 G. Dougan,2 and R. W. Titball1,3

Defence Science and Technology Laboratory, Salisbury, Wiltshire SP4 OJQ,1 Department of Biological Sciences, Centre for Molecular Microbiology and Infection, Imperial College of Science, Technology and Medicine, London SW7 2AY,2 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom3

Received 4 March 2002/ Returned for modification 29 April 2002/ Accepted 4 June 2002

Using a transposon mutagenesis approach, we have identified a mutant of Burkholderia pseudomallei that is auxotrophic for branched chain amino acids. The transposon was shown to have interrupted the ilvI gene encoding the large subunit of the acetolactate synthase enzyme. Compared to the wild type, this mutant was significantly attenuated in a murine model of disease. Mice inoculated intraperitoneally with the auxotrophic mutant, 35 days prior to challenge, were protected against a challenge dose of 6,000 median lethal doses of wild-type B. pseudomallei.

* Corresponding author. Mailing address: Defence Science and Technology Laboratory, CBS Porton Down, Salisbury, Wiltshire SP4 OJQ, United Kingdom. Phone: 44 (1980) 614742. Fax: 44 (1980) 614307. E-mail: TPATKINS{at}dstl.gov.uk.

Editor: A. D. O'Brien

Infection and Immunity, September 2002, p. 5290-5294, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5290-5294.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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