Francisella tularensis subsp. tularensis SCHU S4


Alias: Francisella tularensis Biovar A str. SCHU S4, Francisella tularensis Biovar A str. Schu 4, Francisella tularensis subsp. tularensis Schu 4, Francisella tularensis subsp. tularensis str. SCHU S4, Francisella tularensis subsp. tularensis strain SCHU S4

Top Publications

  1. Michell S, Dean R, Eyles J, Hartley M, Waters E, Prior J, et al. Deletion of the Bacillus anthracis capB homologue in Francisella tularensis subspecies tularensis generates an attenuated strain that protects mice against virulent tularaemia. J Med Microbiol. 2010;59:1275-84 pubmed publisher
    ..These data have important implications for the development of a defined and efficacious tularaemia vaccine. ..
  2. Lindgren H, Honn M, Golovlev I, Kadzhaev K, Conlan W, Sjostedt A. The 58-kilodalton major virulence factor of Francisella tularensis is required for efficient utilization of iron. Infect Immun. 2009;77:4429-36 pubmed publisher
    ..tularensis to utilize iron bound to siderophores and that it likely has a role also in siderophore-independent iron acquisition. We suggest that the FTT0918 protein be designated Fe utilization protein A, FupA. ..
  3. Salomonsson E, Forsberg A, Roos N, Holz C, Maier B, Koomey M, et al. Functional analyses of pilin-like proteins from Francisella tularensis: complementation of type IV pilus phenotypes in Neisseria gonorrhoeae. Microbiology. 2009;155:2546-59 pubmed publisher
    ..Taken together, these findings provide compelling, although indirect, evidence of the potential for Francisella PilA proteins to express functional Tfp. ..
  4. Qin A, Scott D, Thompson J, Mann B. Identification of an essential Francisella tularensis subsp. tularensis virulence factor. Infect Immun. 2009;77:152-61 pubmed publisher
    ..These experiments identified the FTT1103 protein as an essential virulence factor and also demonstrated the feasibility of creating defined attenuated vaccines based on a type A strain. ..
  5. Forslund A, Kuoppa K, Svensson K, Salomonsson E, Johansson A, Bystrom M, et al. Direct repeat-mediated deletion of a type IV pilin gene results in major virulence attenuation of Francisella tularensis. Mol Microbiol. 2006;59:1818-30 pubmed
    ..Our findings indicate that this putative pilin is critical for Francisella infections that occur via peripheral routes. ..
  6. Russo B, Horzempa J, O Dee D, Schmitt D, Brown M, Carlson P, et al. A Francisella tularensis locus required for spermine responsiveness is necessary for virulence. Infect Immun. 2011;79:3665-76 pubmed publisher
    ..These data associate responsiveness to polyamines with tularemia pathogenesis and define FTL_0883/FTT_0615c as an F. tularensis gene important for virulence and evasion of the host immune response...
  7. Baron G, Nano F. MglA and MglB are required for the intramacrophage growth of Francisella novicida. Mol Microbiol. 1998;29:247-59 pubmed
    ..Taken together, these observations suggest that in Francisella MglA and MglB may affect the expression of genes whose products contribute to survival and growth within macrophages...
  8. Batten L, Parnell A, Wells N, Murch A, Oyston P, Roach P. Biochemical and structural characterization of polyphosphate kinase 2 from the intracellular pathogen Francisella tularensis. Biosci Rep. 2015;36:e00294 pubmed publisher
    ..This combination of biochemical, structural and microbiological data provide a sound foundation for future studies targeting the development of PPK2 small molecule inhibitors. ..
  9. Forslund A, Salomonsson E, Golovliov I, Kuoppa K, Michell S, Titball R, et al. The type IV pilin, PilA, is required for full virulence of Francisella tularensis subspecies tularensis. BMC Microbiol. 2010;10:227 pubmed publisher
    ..This suggests that expression and surface localisation of PilA contribute to virulence in the highly virulent type A strain, while PilT was dispensable for virulence in the mouse infection model...

More Information


  1. Zuber M, Hoover T, Dertzbaugh M, Court D. Analysis of the DnaK molecular chaperone system of Francisella tularensis. Gene. 1995;164:149-52 pubmed
    ..The Ft DnaK and DnaJ proteins cross-react with polyclonal antibodies raised against the respective Ec proteins. The grpE-dnaK-dnaJ genes of Ft are organized in a fashion that is more characteristic of Gram+ bacteria. ..
  2. Horzempa J, O Dee D, Shanks R, Nau G. Francisella tularensis DeltapyrF mutants show that replication in nonmacrophages is sufficient for pathogenesis in vivo. Infect Immun. 2010;78:2607-19 pubmed publisher
    ..These findings indicate that replication in nonmacrophages contributes to the pathogenesis of F. tularensis...
  3. Díaz Sáez L, Pankov G, Hunter W. Open and compressed conformations of Francisella tularensis ClpP. Proteins. 2017;85:188-194 pubmed publisher
    ..Our study may now underpin future efforts in a structure-based approach to target ClpP for inhibitor or activator development. Proteins 2016; 85:188-194. © 2016 Wiley Periodicals, Inc. ..
  4. Wu X, Ren G, Gunning W, Weaver D, Kalinoski A, Khuder S, et al. FmvB: A Francisella tularensis Magnesium-Responsive Outer Membrane Protein that Plays a Role in Virulence. PLoS ONE. 2016;11:e0160977 pubmed publisher
    ..tularensis virulence. These results may provide new insights into the importance of magnesium for intracellular pathogens. ..
  5. Qin A, Scott D, Mann B. Francisella tularensis subsp. tularensis Schu S4 disulfide bond formation protein B, but not an RND-type efflux pump, is required for virulence. Infect Immun. 2008;76:3086-92 pubmed publisher
    ..We have shown that DsbB is a key participant in intracellular growth and virulence, and our results suggest that there are critical virulence factors that contain disulfide bonds...
  6. Dai S, Mohapatra N, Schlesinger L, Gunn J. The acid phosphatase AcpA is secreted in vitro and in macrophages by Francisella spp. Infect Immun. 2012;80:1088-97 pubmed publisher
    ..This is the first evidence of acid phosphatase translocation during macrophage infection, and this knowledge will greatly enhance our understanding of the functions of these enzymes in Francisella pathogenesis...
  7. Felts R, Reilly T, Tanner J. Structure of Francisella tularensis AcpA: prototype of a unique superfamily of acid phosphatases and phospholipases C. J Biol Chem. 2006;281:30289-98 pubmed publisher
    ..These results imply a phospholipase C catalytic mechanism that is radically different from that of zinc metallophospholipases...
  8. Keeling P, Doolittle W. Evidence that eukaryotic triosephosphate isomerase is of alpha-proteobacterial origin. Proc Natl Acad Sci U S A. 1997;94:1270-5 pubmed
    ..Among these eukaryotic genes are some from deeply branching, amitochondrial eukaryotes (namely Giardia), which further suggests that this event took place quite early in eukaryotic evolution...
  9. Rohlfing A, Dove S. Coordinate control of virulence gene expression in Francisella tularensis involves direct interaction between key regulators. J Bacteriol. 2014;196:3516-26 pubmed publisher
    ..Our findings uncover a surface of the MglA-SspA complex that is important for interaction with PigR and support the idea that PigR exerts its regulatory effects through an interaction with the RNAP-associated MglA-SspA complex. ..
  10. LoVullo E, Wright L, Isabella V, Huntley J, Pavelka M. Revisiting the Gram-negative lipoprotein paradigm. J Bacteriol. 2015;197:1705-15 pubmed publisher
    ..The paper provides a potential reason for this and shows that it may be widespread in other Gram-negative bacteria. ..
  11. Hu X, Compton J, Abdulhameed M, Marchand C, Robertson K, Leary D, et al. 3-substituted indole inhibitors against Francisella tularensis FabI identified by structure-based virtual screening. J Med Chem. 2013;56:5275-87 pubmed publisher
    ..This residue may affect the stability and closure of the flexible loop to enhance inhibitor (or substrate) binding. ..
  12. Uda A, Sekizuka T, Tanabayashi K, Fujita O, Kuroda M, Hotta A, et al. Role of pathogenicity determinant protein C (PdpC) in determining the virulence of the Francisella tularensis subspecies tularensis SCHU. PLoS ONE. 2014;9:e89075 pubmed publisher
    ..These results demonstrate that PdpC is crucial in determining the virulence of F. tularensis SCHU. ..
  13. Martín García J, Hansen D, Zook J, Loskutov A, Robida M, Craciunescu F, et al. Purification and biophysical characterization of the CapA membrane protein FTT0807 from Francisella tularensis. Biochemistry. 2014;53:1958-70 pubmed publisher
    ..CapA is shown to be an inner-membrane protein and is predicted to play a key cellular role in the assembly of polysaccharides. ..
  14. Shaw G, Li Y, Shi G, Wu Y, Cherry S, Needle D, et al. Structural enzymology and inhibition of the bi-functional folate pathway enzyme HPPK-DHPS from the biowarfare agent Francisella tularensis. FEBS J. 2014;281:4123-37 pubmed publisher
    ..tularensis. The coordinates and structure factors have been deposited in the Protein Data Bank under accession code 4PZV. ..
  15. Egge Jacobsen W, Salomonsson E, Aas F, Forslund A, Winther Larsen H, Maier J, et al. O-linked glycosylation of the PilA pilin protein of Francisella tularensis: identification of the endogenous protein-targeting oligosaccharyltransferase and characterization of the native oligosaccharide. J Bacteriol. 2011;193:5487-97 pubmed publisher
    ..As PglA appears to be highly conserved in Francisella species, O-linked protein glycosylation may be a feature common to members of this genus...
  16. Gutka H, Wolf N, Bondoc J, Movahedzadeh F. Enzymatic Characterization of Fructose 1,6-Bisphosphatase II from Francisella tularensis, an Essential Enzyme for Pathogenesis. Appl Biochem Biotechnol. 2017;183:1439-1454 pubmed publisher
    ..Our findings on the enzyme's properties will facilitate the initial stages of a structure-based drug design program targeting this essential gene of F. tularensis. ..
  17. Thomas R, Twine S, Fulton K, Tessier L, Kilmury S, Ding W, et al. Glycosylation of DsbA in Francisella tularensis subsp. tularensis. J Bacteriol. 2011;193:5498-509 pubmed publisher
    ..This is the first report of the detailed characterization of the DsbA glycan and putative role of the FTT0789-FTT0800 gene cluster in glycan biosynthesis...
  18. Wilkinson R, Batten L, Wells N, Oyston P, Roach P. Biochemical studies on Francisella tularensis RelA in (p)ppGpp biosynthesis. Biosci Rep. 2015;35: pubmed publisher
    ..Activation of F. tularensis RelA by stalled ribosomal complexes formed with ribosomes purified from E. coli MRE600 was observed, but interestingly, significantly weaker activation with ribosomes isolated from Francisella philomiragia. ..
  19. Shakerley N, Chandrasekaran A, Trebak M, Miller B, Melendez J. Francisella tularensis Catalase Restricts Immune Function by Impairing TRPM2 Channel Activity. J Biol Chem. 2016;291:3871-81 pubmed publisher
    ..Together, our findings provide compelling evidence that F. tularensis catalase restricts reactive oxygen species to temper macrophage TRPM2-mediated Ca(2+) signaling and limit host immune function. ..
  20. Child R, Wehrly T, Rockx Brouwer D, Dorward D, Celli J. Acid phosphatases do not contribute to the pathogenesis of type A Francisella tularensis. Infect Immun. 2010;78:59-67 pubmed publisher
    ..Hence, the acid phosphatases AcpA, AcpB, and AcpC do not contribute to intracellular pathogenesis and do not play a major role in the virulence of type A Francisella strains...
  21. Sj stedt A, Sandstr m G, T rnvik A, Jaurin B. Nucleotide sequence and T cell epitopes of a membrane protein of Francisella tularensis. J Immunol. 1990;145:311-7 pubmed
    ..The identified T cell epitopes are presumably relevant to the host defense against F. tularensis, especially because IFN-gamma is known to enhance the antimicrobial activity of the host against intracellular bacteria...
  22. Mdluli K, Anthony L, Baron G, McDonald M, Myltseva S, Nano F. Serum-sensitive mutation of Francisella novicida: association with an ABC transporter gene. Microbiology. 1994;140 ( Pt 12):3309-18 pubmed
    ..We named the corresponding genes in F. novicida, valAB. Integration of a cloned valAB locus into the chromosome of KM14S partially restored the serum resistance phenotype found in wild-type F. novicida...
  23. Leslie D, Cox J, Lee M, Titball R. Analysis of a cloned Francisella tularensis outer membrane protein gene and expression in attenuated Salmonella typhimurium. FEMS Microbiol Lett. 1993;111:331-5 pubmed
    ..fopA was stably maintained in pBluescript in attenuated Salmonella typhimurium where FopA was expressed and located in the outer membrane. This recombinant will be suitable for studies on the role of FopA in immunity against tularaemia. ..
  24. Reilly T, Baron G, Nano F, Kuhlenschmidt M. Characterization and sequencing of a respiratory burst-inhibiting acid phosphatase from Francisella tularensis. J Biol Chem. 1996;271:10973-83 pubmed
    ..Comparative sequence analyses of AcpA is discussed. To our knowledge, this is the first report describing the cloning and sequencing of a burst-inhibiting acid phosphatase...
  25. McDonald M, Cowley S, Nano F. Temperature-sensitive lesions in the Francisella novicida valA gene cloned into an Escherichia coli msbA lpxK mutant affecting deoxycholate resistance and lipopolysaccharide assembly at the restrictive temperature. J Bacteriol. 1997;179:7638-43 pubmed
    ..Also, there was enhanced association of the epitope with the inner membrane after a shift to the nonpermissive temperature. Thus, we propose that ValA is involved in the transport of lipopolysaccharide to the outer membrane...
  26. Johansson A, Ibrahim A, G ransson I, Eriksson U, Gurycova D, Clarridge J, et al. Evaluation of PCR-based methods for discrimination of Francisella species and subspecies and development of a specific PCR that distinguishes the two major subspecies of Francisella tularensis. J Clin Microbiol. 2000;38:4180-5 pubmed
    ..It is proposed that a combination of the specific PCR together with one method generating subspecies-specific patterns is suitable as a rapid and relatively simple strategy for discrimination of Francisella species and subspecies...
  27. Broekhuijsen M, Larsson P, Johansson A, Bystr m M, Eriksson U, Larsson E, et al. Genome-wide DNA microarray analysis of Francisella tularensis strains demonstrates extensive genetic conservation within the species but identifies regions that are unique to the highly virulent F. tularensis subsp. tularensis. J Clin Microbiol. 2003;41:2924-31 pubmed
    ..holarctica and the highly virulent subspecies F. tularensis subsp. tularensis. One of these regions, RD1, allowed for the first time the development of an F. tularensis-specific PCR assay that discriminates each of the four subspecies...
  28. Wang X, Karbarz M, McGrath S, Cotter R, Raetz C. MsbA transporter-dependent lipid A 1-dephosphorylation on the periplasmic surface of the inner membrane: topography of francisella novicida LpxE expressed in Escherichia coli. J Biol Chem. 2004;279:49470-8 pubmed
    ..Our findings provide the first direct evidence that lipid A 1-dephosphorylation catalyzed by LpxE occurs on the periplasmic surface of the inner membrane...
  29. Gilmore R, Bacon R, Sviat S, Petersen J, Bearden S. Identification of Francisella tularensis genes encoding exported membrane-associated proteins using TnphoA mutagenesis of a genomic library. Microb Pathog. 2004;37:205-13 pubmed
    ..tularensis genome sequence data to provide a foundation for studies to identify and define cellular surface protein virulence factors of this pathogen. ..
  30. Maier T, Havig A, Casey M, Nano F, Frank D, Zahrt T. Construction and characterization of a highly efficient Francisella shuttle plasmid. Appl Environ Microbiol. 2004;70:7511-9 pubmed publisher
    ..This new tool should significantly enhance genetic manipulation and characterization of F. tularensis and other Francisella biotypes...
  31. Wang X, McGrath S, Cotter R, Raetz C. Expression cloning and periplasmic orientation of the Francisella novicida lipid A 4'-phosphatase LpxF. J Biol Chem. 2006;281:9321-30 pubmed publisher
    ..The availability of the lpxF gene will facilitate re-engineering lipid A structures in diverse bacteria...
  32. Lee B, Horwitz M, Clemens D. Identification, recombinant expression, immunolocalization in macrophages, and T-cell responsiveness of the major extracellular proteins of Francisella tularensis. Infect Immun. 2006;74:4002-13 pubmed publisher
    ..Finally, we expressed the major culture filtrate proteins that are promising vaccine candidates in Escherichia coli at high levels in soluble form to facilitate study of their immunobiology and potential role in vaccines...
  33. Gil H, Platz G, Forestal C, Monfett M, Bakshi C, Sellati T, et al. Deletion of TolC orthologs in Francisella tularensis identifies roles in multidrug resistance and virulence. Proc Natl Acad Sci U S A. 2006;103:12897-902 pubmed publisher
    ..Thus, tolC is a critical virulence factor of F. tularensis in addition to its role in multidrug resistance, which suggests the presence of a functional type I secretion system...
  34. Mahawar M, Kirimanjeswara G, Metzger D, Bakshi C. Contribution of citrulline ureidase to Francisella tularensis strain Schu S4 pathogenesis. J Bacteriol. 2009;191:4798-806 pubmed publisher
    ..To conclude, this study demonstrates that ctu contributes to intracellular survival, in vivo growth, and pathogenesis. However, ctu is not an absolute requirement for the virulence of F. tularensis Schu S4 in mice...
  35. Sharma J, Mishra B, Li Q, Teale J. TLR4-dependent activation of inflammatory cytokine response in macrophages by Francisella elongation factor Tu. Cell Immunol. 2011;269:69-73 pubmed publisher
    ..This study shows immune stimulatory properties of a cytoplasmic protein EF-Tu expressed on the membrane of virulent Francisella strains...
  36. Brunton J, Steele S, Miller C, LoVullo E, Taft Benz S, Kawula T. Identifying Francisella tularensis genes required for growth in host cells. Infect Immun. 2015;83:3015-25 pubmed publisher
    ..The ΔFTT_0924 mutant was also significantly more sensitive to β-lactam antibiotics than Schu S4. Taken together, the data strongly suggest that FTT_0924 is required for maintaining peptidoglycan integrity and virulence. ..
  37. Wrench A, Gardner C, Siegel S, Pagliai F, Malekiha M, Gonzalez C, et al. MglA/SspA complex interactions are modulated by inorganic polyphosphate. PLoS ONE. 2013;8:e76428 pubmed publisher
    ..3 µM). These observations directly correlated with results obtained from calorimetric scans (DSC), where a strong shift in the mid-transition temperature (Tm) of the MglA/SspA complex was observed in the presence of polyP. ..
  38. Deng K, Blick R, Liu W, Hansen E. Identification of Francisella tularensis genes affected by iron limitation. Infect Immun. 2006;74:4224-36 pubmed publisher
    ..novicida figA mutant to grow under iron-restricted conditions. This study provides the first identification of iron-regulated genes in F. tularensis LVS and evidence for the production of a siderophore-like molecule by F. novicida...
  39. Kingry L, Cummings J, Brookman K, Bommineni G, Tonge P, Slayden R. The Francisella tularensis FabI enoyl-acyl carrier protein reductase gene is essential to bacterial viability and is expressed during infection. J Bacteriol. 2013;195:351-8 pubmed publisher
    ..tularensis is essential and not bypassed by exogenous fatty acids and that de novo fatty acid biosynthetic components encoded in F. tularensis are transcriptionally active during infection in the mouse model of tularemia...
  40. Ziveri J, Tros F, Guerrera I, Chhuon C, Audry M, Dupuis M, et al. The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella. Nat Commun. 2017;8:853 pubmed publisher
    ..Here, Ziveri et al. show that FBA of the pathogen Francisella novicida acts, in addition, as a transcriptional regulator and is important for bacterial multiplication in macrophages. ..