A 55 kDa hypothetical membrane protein is an iron-regulated virulence factor of Francisella tularensis subsp. novicida U112.
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 U112deltaFTT0025 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 deltaFTT0025 mutant was attenuated in a BALB/c mouse model of infection relative to wild-type F. tularensis subsp. novicida U112.
Milne
Timothy S
TS
Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
Michell
Stephen L
SL
Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
Diaper
Helen
H
Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
Wikström
Per
P
Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
Svensson
Kerstin
K
Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
Oyston
Petra C F
PCF
Department of Infection, Immunity and Inflammation, Maurice Shock Building, University of Leicester, PO Box 138, Leicester LE1 9HN, UK.|Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
Titball
Richard W
RW
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.|Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005604:Francisella tularensis / Q000235:genetics / Q000472:pathogenicity*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D020411:Oligonucleotide Array Sequence Analysis; D016019:Survival Analysis; D014406:Tularemia / Q000382:microbiology; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D001426:Bacterial Proteins; D008565:Membrane Proteins; D037521:Virulence Factors; D007501:Iron