A mutant of Burkholderia pseudomallei, auxotrophic in the branched chain amino acid biosynthetic pathway, is attenuated and protective in a murine model of melioidosis.
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.
Defence Science and Technology Laboratory, Salisbury, Wiltshire SP4 OJQ, United Kingdom. TPATKINS@dstl.gov.uk
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T
Atkins
R G
RG
Prior
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K
Mack
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P
Russell
M
M
Nelson
P C F
PC
Oyston
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G
Dougan
R W
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Titball
D000597:Amino Acids, Branched-Chain / Q000096:biosynthesis*; D000818:Animals; D016957:Burkholderia pseudomallei / Q000235:genetics* / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D005260:Female; D005838:Genotype; D008554:Melioidosis / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D010641:Phenotype
D000597:Amino Acids, Branched-Chain