TABLE 3.

F. tularensis subsp. holarctica genes involved in pathogenesis

Locus tagNameFunctionMethod(s)aCells/animals in which mutant strain is attenuatedbReference(s)
FTL_0009FTT1747Outer membrane proteinSTMBALB/c 191
FTL_0010 glpE Thiosulfate sulfurtransferaseSTMBALB/c 191
FTL_0012 recA Recombinase A proteinSTMBALB/c 191
FTL_0028-FTL_0030 carA, carB, pyrBUracil biosynthesisTpMDM 179
FTL_0050FTT1645Hypothetical proteinTpJ774A.1, BALB/c 124
FTL_0058FTT1688Aromatic amino acid transporter of the hydroxy/aromatic amino acid permease familyTpJ774A.1 124
FTL_0073FTT1676Membrane proteinSTMBALB/c 191
FTL_0094 clpB Caseinolytic proteaseAr, Tp, STMBMM, J774A.1c, BALB/c 124, 129, 191
FTL_0111 iglA Intracellular growthSTMBALB/c 191
FTL_0112 iglB Intracellular growthSTMBALB/c 191
FTL_0113 iglC Intracellular growthSTMBALB/c 191
FTL_0113, FTL_1159 iglC1, iglC2Intracellular growth locus CArJ774A.1, PM, PEC, BALB/c 82, 117
FTL_0133 feoB Ferrous iron transport proteinSTMBALB/c 191
FTL_0193 cyoC Cytochrome o-ubiquinol oxidase subunit IIISTMBALB/c 191
FTL_0257 rpmJ 50S ribosomal protein L36STMBALB/c 191
FTL_0304FTT1490Na+/H+ antiporterTpJ774A.1 124
FTL_0337FTT0843UnknownSTMBALB/c 191
FTL_0382 rocE Amino acid permeaseSTMBALB/c 191
FTL_0387 aspC1 Aspartate aminotransferaseSTMBALB/c 191
FTL_0395-FTL_0396 purMCD Purine biosynthesisAr/In, ArJ774A.1, THP-1, PM, A549, BALB/c 145, 146
FTL_0421 tul4 Lipoprotein, T-cell-stimulating antigenSTMBALB/c 191
FTL_0428 parB Chromosome partition protein BSTMBALB/c 191
FTL_0430FTT0910UnknownSTMBALB/c 191
FTL_0439FTT0919Hypothetical outer membrane proteinTpJ774A.1, BALB/c 124
FTL_0439FTT0918UnknownSTMBALB/c 191
FTL_0440FTT0920TransposaseSTMBALB/c 191
FTL_0456 rpsU1 30S ribosomal protein S21STMBALB/c 191
FTL_0483 glgB Glycogen branching enzyme, GlgB; polysaccharide metabolismTp, STMJ774A.1, BALB/c 124, 191
FTL_0485 glgC Glucose-1-phosphate adenylyltransferaseSTMBALB/c 191
FTL_0514FTT1611UnknownSTMBALB/c 191
FTL_0519 minD Division inhibitor ATPaseSTMBALB/c 191
FTL_0520 minC Septum site-determining proteinSTMBALB/c 191
FTL_0525 fumA Fumarate hydrataseSTMBALB/c 191
FTL_0540 lpxB Lipid A-disaccharide synthaseSTMBALB/c 191
FTL_0544FTT1564Hypothetical proteinTpJ774A.1, BALB/c 191
FTL_0552 pmrA Two-component response regulator, orphanAr/InJ774A.1, PM, MH-S, BALB/c, C57BL/6 165
FTL_0584 fadB Acyl coenzyme A binding proteinSTMBALB/c 191
FTL_0589FTT1525cHypothetical membrane proteinSTMBALB/c 191
FTL_0592 wbtA dTDP-glucose 4,6-dehydrataseAr, TpJ774A.1, BALB/c, BALB/cByJ 124, 160, 180, 191
FTL_0594 wbtC UDP-glucose-4-epimeraseTpJ774A.1 124
FTL_0597 wbtF NAD-dependent epimerase, LPS modificationSTMBALB/c 191
FTL_0601 wbtI Sugar transaminase/perosamine synthetasePmBALB/c 115
FTL_0606 wbtM dTDP-glucose 4,6-dehydrataseTpJ774A.1 124
FTL_0616 rpoA2 DNA-directed RNA polymerase, subunitSTMBALB/c 191
FTL_0617 bfr BacterioferritinSTMBALB/c 191
FTL_0645FTT1416cLipoproteinSTMBALB/c 191
FTL_0663FTT1400cUnknownSTMBALB/c 191
FTL_0706FTT1238cHypothetical membrane proteinTpJ774A.1, BALB/c 124
FTL_0723FTT1221UnknownSTMBALB/c 191
FTL_0766 ggt Gamma-glutamyltranspeptidaseTpJ774A.1, RAW, THP-1, BMM, BALB/c 4, 124
FTL_0768 bipA GTP-binding translational elongation factor Tu and G family proteinSTMBALB/c 191
FTL_0789 aspC2 Aspartate aminotransferase, amino acid biosynthesisTp, STMJ774A.1, BALB/c 124, 191
FTL_0803FTT1152UnknownSTMBALB/c 191
FTL_0837 metIQ d-Methionine transport protein (ABC transporter)Tp, STMJ774A.1, BALB/c 124, 191
FTL_0838 metN d-Methionine transport protein (ABC transporter)TpJ774A.1 124
FTL_0846FTT1117cIsochorismatase hydrolase family proteinSTMBALB/c 191
FTL_0878FTT0610DNA/RNA endonuclease familyTpJ774A.1 124
FTL_0886FTT0618cConserved hypothetical protein YleATpJ774A.1, BALB/c 124
FTL_0891 tig Molecular chaperoneSTMBALB/c 191
FTL_0892 clpP ATP-dependent Clp protease subunit PSTMBALB/c 191
FTL_0893 clpX ATP-dependent Clp protease subunit XSTMBALB/c 191
FTL_0894 lon ATP-dependent protease LonSTMBALB/c 191
FTL_0899 hflX Protease, GTP binding subunitSTMBALB/c 191
FTL_0903 hflK Protease modulatorSTMBALB/c 191
FTL_0928 elbB DJ-1/PfpI family proteinSTMBALB/c 191
FTL_0950 rplY 50S ribosomal protein L25STMBALB/c 191
FTL_0960 sthA Soluble pyridine nucleotide transhydrogenaseSTMBALB/c 191
FTL_1029 pilF Type IV pilus lipoproteinArC3H/HeN 25
FTL_1030 rluB Ribosomal large subunit pseudouridine synthase BSTMBALB/c 191
FTL_1071, FTL_1478 guaA, guaBGuanine biosynthesisAr/InJ774, BALB/c 170
FTL_1075FTT1015UnknownSTMBALB/c 191
FTL_1096FTT1103Hypothetical lipoproteinTpJ774A.1, BALB/c 124, 191
FTL_1096FTT1103LipoproteinSTMBALB/c 191
FTL_1097FTT1102Macrophage infectivity potentiatorSTMBALB/c 191
FTL_1134NAMembrane proteinSTMBALB/c 191
FTL_1158, FTL_0112 iglB Intracellular growth locus BArJ774A.1 19
FTL_1225FTT0975UnknownSTMBALB/c 191
FTL_1233FTT0968cAmino acid antiporterSTMBALB/c 191
FTL_1240 aroG Phospho-2-dehydro-3-deoxyheptonate aldolaseSTMBALB/c 191
FTL_1262FTT0945Chorismate family binding protein, aromatic amino acid and folate biosynthesisTpJ774A.1 124
FTL_1266 lipP Lipase/esteraseSTMBALB/c 191
FTL_1273 bioF 8-Amino-7-oxononanoate synthaseSTMBALB/c 191
FTL_1274 bioC Biotin synthesisSTMBALB/c 191
FTL_1275 bioD Dethiobiotin synthetaseSTMBALB/c 191
FTL_1328 fopA Outer membrane-associated proteinSTMBALB/c 191
FTL_1354FTT0759Membrane proteinSTMBALB/c 191
FTL_1392 deaD Cold shock DEAD box protein ASTMBALB/c 191
FTL_1393 ppiC Peptidyl-prolyl cis-trans isomerase or parvulinSTMBALB/c 191
FTL_1404 rplT 50S ribosomal protein L20STMBALB/c 191
FTL_1414 capA Transmembrane HSP60 family proteinSTMBALB/c 191
FTL_1414-FTL_1416 capACB Capsule biosynthesisAr, TpJ774A.1, BALB/c 124, 191
FTL_1415 capC Capsular polyglutamate biosynthesis protein CapCSTMBALB/c 191
FTL_1416 capB Capsular polyglutamate biosynthesis protein CapBSTMBALB/c 191
FTL_1419 cphB CyanophycinaseSTMBALB/c 191
FTL_1452 rpmA 50S ribosomal protein L27STMBALB/c 191
FTL_1458 secA Preprotein translocase, subunit ASTMBALB/c 191
FTL_1461 deoD Purine nucleoside phosphorylaseSTMBALB/c 191
FTL_1473 uvrA DNA excision repair enzyme, subunit ASTMBALB/c 191
FTL_1474 greA Transcription elongation factorSTMBALB/c 191
FTL_1475FTT1314cType IV pilus fiber building block proteinSTMBALB/c 191
FTL_1504 katG CatalaseSTMBALB/c 191
FTL_1528FTT0708Major facilitator superfamily transport proteinSTMBALB/c 191
FTL_1542 migR Transcriptional regulatorArMDM 22
FTL_1553 sucC Succinyl coenzyme A synthetase beta chainSTMBALB/c 191
FTL_1554 sucD Succinyl coenzyme A synthetase alpha chainSTMBALB/c 191
FTL_1581 tivA Hypothetical lipoproteinAr/InCE, MDM 93
FTL_1583 xasA Glutamate-aminobutyric acid antiporter, XasA; amino acid transportTpJ774A.1 124
FTL_1601 yibK tRNA/rRNA methyltransferaseSTMBALB/c 191
FTL_1622FTT0444Multidrug transporterSTMBALB/c 191
FTL_1623FTT0443UnknownSTMBALB/c 191
FTL_1664 deoB PhosphopentomutaseAr/InCE, MDM, DC, HEK-293 93
FTL_1670 dsbB Disulfide bond formation protein, DsbBTpJ774A.1 124
FTL_1672 acrB RND efflux pumpIn, STMBALB/c 15, 191
FTL_1678FTT0101Membrane proteinSTMBALB/c 191
FTL_1701 gplX Fructose-1,6-bisphosphataseTp, STMJ774A.1, BALB/c 124, 191
FTL_1750 secE Preprotein translocase, subunit ESTMBALB/c 191
FTL_1771 pilT Twitching motility protein PilTTpC3H/HeN 25
FTL_1793 sodB Fe-superoxide dismutaseArBALB/c, C57BL/6, MH-S 9
FTL_1806FTT0053Major facilitator superfamily transporterTpJ774A.1 124
FTL_1832FTT0029cUnknownSTMBALB/c 191
FTL_1865 tolC Glutamate decarboxylaseArC3H/HeN 77
FTL_1867 yegQ ProteaseSTMBALB/c 191
FTL_1912 rpsA 30S ribosomal protein S1STMBALB/c 191
FTL_1914 ripA Hypothetical proteinArJ774A.1, TC-1, C57BL/6 72
FTL_1936FTT0209cPeriplasmic solute binding family proteinSTMBALB/c 191
FTL_1947 yjjk ABC transporter ATP binding proteinSTMBALB/c 191
FTL_R000316S rRNA16S rRNASTMBALB/c 191
FTL_R0004tRNA-IletRNA-isoleucineSTMBALB/c 191
FTT0890 pilA Type IV pilus fiber building block proteinRecomb.C57BL/6 65
  • a Ar, allelic replacement; In, insertion; Tp, transposon insertion; STM, signature-tagged mutagenesis; Recomb., direct repeat-mediated deletion.

  • b MDM, monocyte-derived macrophages; PM, peritoneal macrophages; PEC, peritoneal exudate cells; CE, chicken embryos; DC, dendritic cells.

  • c Intermediate attenuation phenotype.