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Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Virulence difference between the prototypic Schu S4 strain (A1a) and Francisella tularensisA1a, A1b, A2 and type B strains in a murine model of infection

Authors: Claudia R Molins, Mark J Delorey, Brook M Yockey, John W Young, John T Belisle, Martin E Schriefer, Jeannine M Petersen

Published in: BMC Infectious Diseases | Issue 1/2014

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Abstract

Background

The use of prototypic strains is common among laboratories studying infectious agents as it promotes consistency for data comparability among and between laboratories. Schu S4 is the prototypic virulent strain of Francisella tularensis and has been used extensively as such over the past six decades. Studies have demonstrated virulence differences among the two clinically relevant subspecies of F. tularensis, tularensis (type A) and holarctica (type B) and more recently between type A subpopulations (A1a, A1b and A2). Schu S4 belongs to the most virulent subspecies of F. tularensis, subspecies tularensis.

Methods

In this study, we investigated the relative virulence of Schu S4 in comparison to A1a, A1b, A2 and type B strains using a temperature-based murine model of infection. Mice were inoculated intradermally and a hypothermic drop point was used as a surrogate for death. Survival curves and the length of temperature phases were compared for all infections. Bacterial burdens were also compared between the most virulent type A subpopulation, A1b, and Schu S4 at drop point.

Results

Survival curve comparisons demonstrate that the Schu S4 strain used in this study resembles the virulence of type B strains, and is significantly less virulent than all other type A (A1a, A1b and A2) strains tested. Additionally, when bacterial burdens were compared between mice infected with Schu S4 or MA00-2987 (A1b) significantly higher burdens were present in the blood and spleen of mice infected with MA00-2987.

Conclusions

The knowledge gained from using Schu S4 as a prototypic virulent strain has unquestionably advanced the field of tularemia research. The findings of this study, however, indicate that careful consideration of F. tularensis strain selection must occur when the overall virulence of the strain used could impact the outcome and interpretation of results.
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Literature
1.
go back to reference Wherry WB, Lamb BH: Infection of man with Bacterium tularense. J Infect Dis. 1914, 15: 331-340. 10.1093/infdis/15.2.331.CrossRef Wherry WB, Lamb BH: Infection of man with Bacterium tularense. J Infect Dis. 1914, 15: 331-340. 10.1093/infdis/15.2.331.CrossRef
3.
go back to reference Downs CM, Woodward JM: Studies on pathogenesis and immunity in tularemia III. Immunogenic properties for the white mouse of various strains of Bacterium tularense. J Immunol. 1949, 63: 147-163.PubMed Downs CM, Woodward JM: Studies on pathogenesis and immunity in tularemia III. Immunogenic properties for the white mouse of various strains of Bacterium tularense. J Immunol. 1949, 63: 147-163.PubMed
4.
go back to reference Olsufiev NG, Emelyanova OS, Dunayeva TN: Comparative study of strains of B. tularense in the old and new world and their taxonomy. J Hyg Epidemiol Microbiol Immunol. 1959, 3: 138-149.PubMed Olsufiev NG, Emelyanova OS, Dunayeva TN: Comparative study of strains of B. tularense in the old and new world and their taxonomy. J Hyg Epidemiol Microbiol Immunol. 1959, 3: 138-149.PubMed
5.
go back to reference Olsufyev NG, Emelyanova OS: Further studies of strains of tularemic bacteria of the old and new world. J Hyg Epidemiol Microbiol Immunol. 1962, 6: 193-205.PubMed Olsufyev NG, Emelyanova OS: Further studies of strains of tularemic bacteria of the old and new world. J Hyg Epidemiol Microbiol Immunol. 1962, 6: 193-205.PubMed
6.
go back to reference Eigelsbach HT, Braun W, Herring RD: Studies on the variation of Bacterium tularense. J Bacteriol. 1951, 5: 557-569. Eigelsbach HT, Braun W, Herring RD: Studies on the variation of Bacterium tularense. J Bacteriol. 1951, 5: 557-569.
7.
go back to reference Larsson P, Oyston PCF, Chain P, Chu MC, Duffield M, Fuxelius H, Garcia E, Hälltorp G, Johansson D, Isherwood KE, Karp PD, Larsson E, Liu Y, Michell S, Prior J, Prior R, Malfatti S, Sjöstedt A, Svensson K, Thompson N, Vergez L, Wagg JK, Wren BW, Lindler LE, Andersson SGE, Forsman M, Titball RW: The complete genome sequence of Francisella tularensis, the causative agent of tularemia. Nat Genet. 2005, 37: 153-159. 10.1038/ng1499.CrossRefPubMed Larsson P, Oyston PCF, Chain P, Chu MC, Duffield M, Fuxelius H, Garcia E, Hälltorp G, Johansson D, Isherwood KE, Karp PD, Larsson E, Liu Y, Michell S, Prior J, Prior R, Malfatti S, Sjöstedt A, Svensson K, Thompson N, Vergez L, Wagg JK, Wren BW, Lindler LE, Andersson SGE, Forsman M, Titball RW: The complete genome sequence of Francisella tularensis, the causative agent of tularemia. Nat Genet. 2005, 37: 153-159. 10.1038/ng1499.CrossRefPubMed
8.
go back to reference Farlow J, Smith KL, Wong J, Abrams M, Lytle M, Keim P: Francisella tularensis strain typing using multiple-locus, variable-number tandem repeat analysis. J Clin Microbiol. 2001, 39: 3186-3192. 10.1128/JCM.39.9.3186-3192.2001.CrossRefPubMedPubMedCentral Farlow J, Smith KL, Wong J, Abrams M, Lytle M, Keim P: Francisella tularensis strain typing using multiple-locus, variable-number tandem repeat analysis. J Clin Microbiol. 2001, 39: 3186-3192. 10.1128/JCM.39.9.3186-3192.2001.CrossRefPubMedPubMedCentral
9.
go back to reference Johansson A, Farlow J, Larsson P, Dukerich M, Chambers E, Byström M, Fox J, Chu M, Forsman M, Sjöstedt A, Keim P: Worldwide genetic relationships among Francisella tularensis isolates determined by multiple-locus variable-number tandem repeat analysis. J Bacteriol. 2004, 186: 5808-5818. 10.1128/JB.186.17.5808-5818.2004.CrossRefPubMedPubMedCentral Johansson A, Farlow J, Larsson P, Dukerich M, Chambers E, Byström M, Fox J, Chu M, Forsman M, Sjöstedt A, Keim P: Worldwide genetic relationships among Francisella tularensis isolates determined by multiple-locus variable-number tandem repeat analysis. J Bacteriol. 2004, 186: 5808-5818. 10.1128/JB.186.17.5808-5818.2004.CrossRefPubMedPubMedCentral
10.
go back to reference Pandya GA, Holmes MH, Petersen JM, Pradhan S, Karamycheva SA, Wolcott MJ, Molins C, Jones M, Schriefer ME, Fleischmann RD, Peterson SN: Whole genome single nucleotide polymorphism based phylogeny of Francisella tularensis and its application to the development of a strain typing assay. BMC Microbiol. 2009, 9: 213-10.1186/1471-2180-9-213. doi:10.1186/1471-2180-9-213CrossRefPubMedPubMedCentral Pandya GA, Holmes MH, Petersen JM, Pradhan S, Karamycheva SA, Wolcott MJ, Molins C, Jones M, Schriefer ME, Fleischmann RD, Peterson SN: Whole genome single nucleotide polymorphism based phylogeny of Francisella tularensis and its application to the development of a strain typing assay. BMC Microbiol. 2009, 9: 213-10.1186/1471-2180-9-213. doi:10.1186/1471-2180-9-213CrossRefPubMedPubMedCentral
11.
go back to reference Staples JE, Kubota KA, Chalcraft LG, Mead PS, Petersen JM: Epidemiologic and molecular analysis of human tularemia, United States, 1964–2004. Emerg Infect Dis. 2006, 12: 1113-1118. 10.3201/eid1207.051504.CrossRefPubMedPubMedCentral Staples JE, Kubota KA, Chalcraft LG, Mead PS, Petersen JM: Epidemiologic and molecular analysis of human tularemia, United States, 1964–2004. Emerg Infect Dis. 2006, 12: 1113-1118. 10.3201/eid1207.051504.CrossRefPubMedPubMedCentral
12.
go back to reference Svensson K, Larsson P, Johansson D, Byström M, Forsman M, Johansson A: Evolution of subspecies of Francisella tularensis. J Bacteriol. 2005, 187: 3903-3908. 10.1128/JB.187.11.3903-3908.2005.CrossRefPubMedPubMedCentral Svensson K, Larsson P, Johansson D, Byström M, Forsman M, Johansson A: Evolution of subspecies of Francisella tularensis. J Bacteriol. 2005, 187: 3903-3908. 10.1128/JB.187.11.3903-3908.2005.CrossRefPubMedPubMedCentral
13.
go back to reference Vogler AJ, Birdsell D, Price LB, Bowers JR, Beckstrom-Sternberg SM, Auerbach RK, Beckstrom-Sternberg JS, Johansson A, Clare A, Buchhagen JL, Petersen JM, Pearson T, Vaissaire J, Dempsey MP, Foxall P, Engelthaler DM, Wagner DM, Keim P: Phylogeography of Francisella tularensis: global expansion of a highly fit clone. J Bacteriol. 2009, 8: 2474-2484.CrossRef Vogler AJ, Birdsell D, Price LB, Bowers JR, Beckstrom-Sternberg SM, Auerbach RK, Beckstrom-Sternberg JS, Johansson A, Clare A, Buchhagen JL, Petersen JM, Pearson T, Vaissaire J, Dempsey MP, Foxall P, Engelthaler DM, Wagner DM, Keim P: Phylogeography of Francisella tularensis: global expansion of a highly fit clone. J Bacteriol. 2009, 8: 2474-2484.CrossRef
14.
go back to reference Kugeler KJ, Mead PS, Janusz AM, Staples JE, Kubota KA, Chalcraft LG, Petersen JM: Molecular epidemiology of Francisella tularensis in the United States. Clin Infect Dis. 2009, 48: 863-870. 10.1086/597261.CrossRefPubMed Kugeler KJ, Mead PS, Janusz AM, Staples JE, Kubota KA, Chalcraft LG, Petersen JM: Molecular epidemiology of Francisella tularensis in the United States. Clin Infect Dis. 2009, 48: 863-870. 10.1086/597261.CrossRefPubMed
15.
go back to reference Petersen JM, Molins CR: Subpopulations of Francisella tularensis ssp. tularensis and holarctica: identification and associated epidemiology. Future Microbiol. 2010, 5: 649-661. 10.2217/fmb.10.17.CrossRefPubMed Petersen JM, Molins CR: Subpopulations of Francisella tularensis ssp. tularensis and holarctica: identification and associated epidemiology. Future Microbiol. 2010, 5: 649-661. 10.2217/fmb.10.17.CrossRefPubMed
16.
go back to reference Molins CR, Delorey MJ, Yockey BM, Young JW, Sheldon SW, Reese SM, Schriefer ME, Petersen JM: Virulence differences among Francisella tularensis subsp. tularensis clades in mice. PLoS One. 2010, 5: e10205-10.1371/journal.pone.0010205. 10.1371/journal.pone.0010205CrossRefPubMedPubMedCentral Molins CR, Delorey MJ, Yockey BM, Young JW, Sheldon SW, Reese SM, Schriefer ME, Petersen JM: Virulence differences among Francisella tularensis subsp. tularensis clades in mice. PLoS One. 2010, 5: e10205-10.1371/journal.pone.0010205. 10.1371/journal.pone.0010205CrossRefPubMedPubMedCentral
17.
go back to reference Twine SM, Shen H, Kelly JF, Chen W, Sjöstedt A, Conlan JW: Virulence comparison in mice of distinct isolates of type A Francisella tularensis. Microb Pathog. 2006, 4: 133-138.CrossRef Twine SM, Shen H, Kelly JF, Chen W, Sjöstedt A, Conlan JW: Virulence comparison in mice of distinct isolates of type A Francisella tularensis. Microb Pathog. 2006, 4: 133-138.CrossRef
18.
go back to reference Molins CR, Delorey MJ, Young JW, Yockey BM, Belisle JT, Schriefer ME, Petersen JM: Use of temperature for standardizing the progression of Francisella tularensis in mice. PLoS One. 2012, 7: e45310-10.1371/journal.pone.0045310. doi:10.1371/journal.pone.0045310CrossRefPubMedPubMedCentral Molins CR, Delorey MJ, Young JW, Yockey BM, Belisle JT, Schriefer ME, Petersen JM: Use of temperature for standardizing the progression of Francisella tularensis in mice. PLoS One. 2012, 7: e45310-10.1371/journal.pone.0045310. doi:10.1371/journal.pone.0045310CrossRefPubMedPubMedCentral
19.
go back to reference National Research Council: Guide for the care and use of laboratory animals. 1996, Washington D.C: National Academy Press, 1-118. National Research Council: Guide for the care and use of laboratory animals. 1996, Washington D.C: National Academy Press, 1-118.
20.
go back to reference Bell JF, Owen CR, Larson CL: Virulence of Bacterium tularense. I. A study of the virulence of Bacterium tularense in mice, guinea pigs, and rabbits. J Infect Dis. 1955, 97: 162-166. 10.1093/infdis/97.2.162.CrossRefPubMed Bell JF, Owen CR, Larson CL: Virulence of Bacterium tularense. I. A study of the virulence of Bacterium tularense in mice, guinea pigs, and rabbits. J Infect Dis. 1955, 97: 162-166. 10.1093/infdis/97.2.162.CrossRefPubMed
Metadata
Title
Virulence difference between the prototypic Schu S4 strain (A1a) and Francisella tularensisA1a, A1b, A2 and type B strains in a murine model of infection
Authors
Claudia R Molins
Mark J Delorey
Brook M Yockey
John W Young
John T Belisle
Martin E Schriefer
Jeannine M Petersen
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-67

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