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

BMC Infectious Diseases

Jeannine M Petersen²  Martin E Schriefer²  John T Belisle¹  John W Young²  Brook M Yockey²  Mark J Delorey²  Claudia R Molins² 

[1] Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523 USA;Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Bacterial Diseases Branch, 3156 Rampart Road, Fort Collins, CO 80521 USA

关键词: A1a;    Schu S₄;    Tularemia;    Francisella tularensis;    Fever;    Murine model;    Prototypic strains;   

Others  :  1134749
DOI  :  10.1186/1471-2334-14-67

 received in 2013-09-26, accepted in 2014-01-28,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Molins et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Wherry WB, Lamb BH: Infection of man with Bacterium tularense. J Infect Dis 1914, 15:331-340.
• [2]Hesselbrock W, Foshay L: The morphology of Bacterium tularense. J Bacteriol 1945, 49:209-231.
• [3]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.
• [4]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.
• [5]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.
• [6]Eigelsbach HT, Braun W, Herring RD: Studies on the variation of Bacterium tularense. J Bacteriol 1951, 5:557-569.
• [7]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.
• [8]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.
• [9]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]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. doi:10.1186/1471-2180-9-213 BioMed Central Full Text
• [11]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.
• [12]Svensson K, Larsson P, Johansson D, Byström M, Forsman M, Johansson A: Evolution of subspecies of Francisella tularensis. J Bacteriol 2005, 187:3903-3908.
• [13]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.
• [14]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.
• [15]Petersen JM, Molins CR: Subpopulations of Francisella tularensis ssp. tularensis and holarctica: identification and associated epidemiology. Future Microbiol 2010, 5:649-661.
• [16]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
• [17]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.
• [18]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. doi:10.1371/journal.pone.0045310
• [19]National Research Council: Guide for the care and use of laboratory animals. Washington D.C: National Academy Press; 1996:1-118.
• [20]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.