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J Med Microbiol 56 (2007), 1268-1276; DOI: 10.1099/jmm.0.47190-0
© 2007 Society for General Microbiology
ISSN 1473-5644

A 55 kDa hypothetical membrane protein is an iron-regulated virulence factor of Francisella tularensis subsp. novicida U112

Timothy S. Milne1, Stephen L. Michell1,{dagger}, Helen Diaper1, Per Wikström2, Kerstin Svensson2, Petra C. F. Oyston1,3 and Richard W. Titball1,4,{dagger}

1 Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK

2 Swedish Defence Research Agency, SE-901 82 Umeå, Sweden

3 Department of Infection, Immunity and Inflammation, Maurice Shock Building, University of Leicester, PO Box 138, Leicester LE1 9HN, UK

4 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

Correspondence
Timothy S. Milne
TSMILNE{at}dstl.gov.uk

Received 26 January 2007
Accepted 13 June 2007

Iron is an important nutritional requirement for bacteria due to its conserved role in many essential metabolic processes. As a consequence of the lack of freely available iron in the mammalian host, bacteria upregulate a range of virulence factors during infection. Transcriptional analysis of Francisella tularensis subsp. novicida U112 grown in iron-deficient medium identified 21 genes upregulated in response to this condition, four of which were attributed to a siderophore operon. In addition, a novel iron-regulated gene, FTT0025, was identified which is part of this operon and encodes a 55 kDa hypothetical membrane protein. When grown on chrome azurol S agar, the F. tularensis subsp. novicida U112{Delta}FTT0025 mutant produced an increased reaction zone compared with the wild-type, suggesting that siderophore production was unaffected but that the bacteria may have a deficiency in their ability to re-sequester this iron-binding molecule. Furthermore, the {Delta}FTT0025 mutant was attenuated in a BALB/c mouse model of infection relative to wild-type F. tularensis subsp. novicida U112.

Abbreviations: CAS, chrome azurol S; LVS, live vaccine strain; MLD, median lethal dose; s.c., subcutaneous.

{dagger}Present address: School of Biosciences, Geoffrey Pope Building, University of Exeter, Exeter EX4 4QD, UK.






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