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/c191
FTL_0010glpEThiosulfate sulfurtransferaseSTMBALB/c191
FTL_0012recARecombinase A proteinSTMBALB/c191
FTL_0028-FTL_0030carA, carB, pyrBUracil biosynthesisTpMDM179
FTL_0050FTT1645Hypothetical proteinTpJ774A.1, BALB/c124
FTL_0058FTT1688Aromatic amino acid transporter of the hydroxy/aromatic amino acid permease familyTpJ774A.1124
FTL_0073FTT1676Membrane proteinSTMBALB/c191
FTL_0094clpBCaseinolytic proteaseAr, Tp, STMBMM, J774A.1c, BALB/c124, 129, 191
FTL_0111iglAIntracellular growthSTMBALB/c191
FTL_0112iglBIntracellular growthSTMBALB/c191
FTL_0113iglCIntracellular growthSTMBALB/c191
FTL_0113, FTL_1159iglC1, iglC2Intracellular growth locus CArJ774A.1, PM, PEC, BALB/c82, 117
FTL_0133feoBFerrous iron transport proteinSTMBALB/c191
FTL_0193cyoCCytochrome o-ubiquinol oxidase subunit IIISTMBALB/c191
FTL_0257rpmJ50S ribosomal protein L36STMBALB/c191
FTL_0304FTT1490Na+/H+ antiporterTpJ774A.1124
FTL_0337FTT0843UnknownSTMBALB/c191
FTL_0382rocEAmino acid permeaseSTMBALB/c191
FTL_0387aspC1Aspartate aminotransferaseSTMBALB/c191
FTL_0395-FTL_0396purMCDPurine biosynthesisAr/In, ArJ774A.1, THP-1, PM, A549, BALB/c145, 146
FTL_0421tul4Lipoprotein, T-cell-stimulating antigenSTMBALB/c191
FTL_0428parBChromosome partition protein BSTMBALB/c191
FTL_0430FTT0910UnknownSTMBALB/c191
FTL_0439FTT0919Hypothetical outer membrane proteinTpJ774A.1, BALB/c124
FTL_0439FTT0918UnknownSTMBALB/c191
FTL_0440FTT0920TransposaseSTMBALB/c191
FTL_0456rpsU130S ribosomal protein S21STMBALB/c191
FTL_0483glgBGlycogen branching enzyme, GlgB; polysaccharide metabolismTp, STMJ774A.1, BALB/c124, 191
FTL_0485glgCGlucose-1-phosphate adenylyltransferaseSTMBALB/c191
FTL_0514FTT1611UnknownSTMBALB/c191
FTL_0519minDDivision inhibitor ATPaseSTMBALB/c191
FTL_0520minCSeptum site-determining proteinSTMBALB/c191
FTL_0525fumAFumarate hydrataseSTMBALB/c191
FTL_0540lpxBLipid A-disaccharide synthaseSTMBALB/c191
FTL_0544FTT1564Hypothetical proteinTpJ774A.1, BALB/c191
FTL_0552pmrATwo-component response regulator, orphanAr/InJ774A.1, PM, MH-S, BALB/c, C57BL/6165
FTL_0584fadBAcyl coenzyme A binding proteinSTMBALB/c191
FTL_0589FTT1525cHypothetical membrane proteinSTMBALB/c191
FTL_0592wbtAdTDP-glucose 4,6-dehydrataseAr, TpJ774A.1, BALB/c, BALB/cByJ124, 160, 180, 191
FTL_0594wbtCUDP-glucose-4-epimeraseTpJ774A.1124
FTL_0597wbtFNAD-dependent epimerase, LPS modificationSTMBALB/c191
FTL_0601wbtISugar transaminase/perosamine synthetasePmBALB/c115
FTL_0606wbtMdTDP-glucose 4,6-dehydrataseTpJ774A.1124
FTL_0616rpoA2DNA-directed RNA polymerase, subunitSTMBALB/c191
FTL_0617bfrBacterioferritinSTMBALB/c191
FTL_0645FTT1416cLipoproteinSTMBALB/c191
FTL_0663FTT1400cUnknownSTMBALB/c191
FTL_0706FTT1238cHypothetical membrane proteinTpJ774A.1, BALB/c124
FTL_0723FTT1221UnknownSTMBALB/c191
FTL_0766ggtGamma-glutamyltranspeptidaseTpJ774A.1, RAW, THP-1, BMM, BALB/c4, 124
FTL_0768bipAGTP-binding translational elongation factor Tu and G family proteinSTMBALB/c191
FTL_0789aspC2Aspartate aminotransferase, amino acid biosynthesisTp, STMJ774A.1, BALB/c124, 191
FTL_0803FTT1152UnknownSTMBALB/c191
FTL_0837metIQd-Methionine transport protein (ABC transporter)Tp, STMJ774A.1, BALB/c124, 191
FTL_0838metNd-Methionine transport protein (ABC transporter)TpJ774A.1124
FTL_0846FTT1117cIsochorismatase hydrolase family proteinSTMBALB/c191
FTL_0878FTT0610DNA/RNA endonuclease familyTpJ774A.1124
FTL_0886FTT0618cConserved hypothetical protein YleATpJ774A.1, BALB/c124
FTL_0891tigMolecular chaperoneSTMBALB/c191
FTL_0892clpPATP-dependent Clp protease subunit PSTMBALB/c191
FTL_0893clpXATP-dependent Clp protease subunit XSTMBALB/c191
FTL_0894lonATP-dependent protease LonSTMBALB/c191
FTL_0899hflXProtease, GTP binding subunitSTMBALB/c191
FTL_0903hflKProtease modulatorSTMBALB/c191
FTL_0928elbBDJ-1/PfpI family proteinSTMBALB/c191
FTL_0950rplY50S ribosomal protein L25STMBALB/c191
FTL_0960sthASoluble pyridine nucleotide transhydrogenaseSTMBALB/c191
FTL_1029pilFType IV pilus lipoproteinArC3H/HeN25
FTL_1030rluBRibosomal large subunit pseudouridine synthase BSTMBALB/c191
FTL_1071, FTL_1478guaA, guaBGuanine biosynthesisAr/InJ774, BALB/c170
FTL_1075FTT1015UnknownSTMBALB/c191
FTL_1096FTT1103Hypothetical lipoproteinTpJ774A.1, BALB/c124, 191
FTL_1096FTT1103LipoproteinSTMBALB/c191
FTL_1097FTT1102Macrophage infectivity potentiatorSTMBALB/c191
FTL_1134NAMembrane proteinSTMBALB/c191
FTL_1158, FTL_0112iglBIntracellular growth locus BArJ774A.119
FTL_1225FTT0975UnknownSTMBALB/c191
FTL_1233FTT0968cAmino acid antiporterSTMBALB/c191
FTL_1240aroGPhospho-2-dehydro-3-deoxyheptonate aldolaseSTMBALB/c191
FTL_1262FTT0945Chorismate family binding protein, aromatic amino acid and folate biosynthesisTpJ774A.1124
FTL_1266lipPLipase/esteraseSTMBALB/c191
FTL_1273bioF8-Amino-7-oxononanoate synthaseSTMBALB/c191
FTL_1274bioCBiotin synthesisSTMBALB/c191
FTL_1275bioDDethiobiotin synthetaseSTMBALB/c191
FTL_1328fopAOuter membrane-associated proteinSTMBALB/c191
FTL_1354FTT0759Membrane proteinSTMBALB/c191
FTL_1392deaDCold shock DEAD box protein ASTMBALB/c191
FTL_1393ppiCPeptidyl-prolyl cis-trans isomerase or parvulinSTMBALB/c191
FTL_1404rplT50S ribosomal protein L20STMBALB/c191
FTL_1414capATransmembrane HSP60 family proteinSTMBALB/c191
FTL_1414-FTL_1416capACBCapsule biosynthesisAr, TpJ774A.1, BALB/c124, 191
FTL_1415capCCapsular polyglutamate biosynthesis protein CapCSTMBALB/c191
FTL_1416capBCapsular polyglutamate biosynthesis protein CapBSTMBALB/c191
FTL_1419cphBCyanophycinaseSTMBALB/c191
FTL_1452rpmA50S ribosomal protein L27STMBALB/c191
FTL_1458secAPreprotein translocase, subunit ASTMBALB/c191
FTL_1461deoDPurine nucleoside phosphorylaseSTMBALB/c191
FTL_1473uvrADNA excision repair enzyme, subunit ASTMBALB/c191
FTL_1474greATranscription elongation factorSTMBALB/c191
FTL_1475FTT1314cType IV pilus fiber building block proteinSTMBALB/c191
FTL_1504katGCatalaseSTMBALB/c191
FTL_1528FTT0708Major facilitator superfamily transport proteinSTMBALB/c191
FTL_1542migRTranscriptional regulatorArMDM22
FTL_1553sucCSuccinyl coenzyme A synthetase beta chainSTMBALB/c191
FTL_1554sucDSuccinyl coenzyme A synthetase alpha chainSTMBALB/c191
FTL_1581tivAHypothetical lipoproteinAr/InCE, MDM93
FTL_1583xasAGlutamate-aminobutyric acid antiporter, XasA; amino acid transportTpJ774A.1124
FTL_1601yibKtRNA/rRNA methyltransferaseSTMBALB/c191
FTL_1622FTT0444Multidrug transporterSTMBALB/c191
FTL_1623FTT0443UnknownSTMBALB/c191
FTL_1664deoBPhosphopentomutaseAr/InCE, MDM, DC, HEK-29393
FTL_1670dsbBDisulfide bond formation protein, DsbBTpJ774A.1124
FTL_1672acrBRND efflux pumpIn, STMBALB/c15, 191
FTL_1678FTT0101Membrane proteinSTMBALB/c191
FTL_1701gplXFructose-1,6-bisphosphataseTp, STMJ774A.1, BALB/c124, 191
FTL_1750secEPreprotein translocase, subunit ESTMBALB/c191
FTL_1771pilTTwitching motility protein PilTTpC3H/HeN25
FTL_1793sodBFe-superoxide dismutaseArBALB/c, C57BL/6, MH-S9
FTL_1806FTT0053Major facilitator superfamily transporterTpJ774A.1124
FTL_1832FTT0029cUnknownSTMBALB/c191
FTL_1865tolCGlutamate decarboxylaseArC3H/HeN77
FTL_1867yegQProteaseSTMBALB/c191
FTL_1912rpsA30S ribosomal protein S1STMBALB/c191
FTL_1914ripAHypothetical proteinArJ774A.1, TC-1, C57BL/672
FTL_1936FTT0209cPeriplasmic solute binding family proteinSTMBALB/c191
FTL_1947yjjkABC transporter ATP binding proteinSTMBALB/c191
FTL_R000316S rRNA16S rRNASTMBALB/c191
FTL_R0004tRNA-IletRNA-isoleucineSTMBALB/c191
FTT0890pilAType IV pilus fiber building block proteinRecomb.C57BL/665
  • 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.