Identification of an Attenuated Substrain of Francisella tularensis SCHU S4 by Phenotypic and Genotypic Analyses

Lovchik, Julie A.; Reed, Douglas S.; Hutt, Julie A.; Xia, Fangfang; Stevens, Rick L.; Modise, Thero; Barry, Eileen M.; Wu, Terry H.

doi:10.3390/pathogens10060638

Title: Identification of an Attenuated Substrain of Francisella tularensis SCHU S4 by Phenotypic and Genotypic Analyses

Journal Article · Sat May 22 00:00:00 EDT 2021 · Pathogens

DOI:https://doi.org/10.3390/pathogens10060638· OSTI ID:1787299

Lovchik, Julie A. ^[1];

^[2]; Hutt, Julie A. ^[3];

^[4]; Stevens, Rick L. ^[5]; Modise, Thero ^[6]; Barry, Eileen M. ^[7];

^[1]

Univ. of New Mexico Health Sciences Center, Albuquerque, NM (United States)
Univ. of Pittsburgh, PA (United States)
Lovelace Respiratory Research Inst., Albuquerque, NM (United States)
Argonne National Lab. (ANL), Argonne, IL (United States)
Argonne National Lab. (ANL), Argonne, IL (United States); Univ. of Chicago, IL (United States)
Univ. of Botswana, Gaborone (Botswana)
Univ. of Maryland School of Medicine, Baltimore, MD (United States)

Pneumonic tularemia is a highly debilitating and potentially fatal disease caused by inhalation of Francisella tularensis. Most of our current understanding of its pathogenesis is based on the highly virulent F. tularensis subsp. tularensis strain SCHU S4. However, multiple sources of SCHU S4 have been maintained and propagated independently over the years, potentially generating genetic variants with altered virulence. In this study, the virulence of four SCHU S4 stocks (NR-10492, NR-28534, NR-643 from BEI Resources and FTS-635 from Battelle Memorial Institute) along with another virulent subsp. tularensis strain, MA00-2987, were assessed in parallel. In the Fischer 344 rat model of pneumonic tularemia, NR-643 and FTS-635 were found to be highly attenuated compared to NR-10492, NR-28534, and MA00-2987. In the NZW rabbit model of pneumonic tularemia, NR-643 caused morbidity but not mortality even at a dose equivalent to 500x the LD₅₀ for NR-10492. Genetic analyses revealed that NR-10492 and NR-28534 were identical to each other, and nearly identical to the reference SCHU S4 sequence. NR-643 and FTS-635 were identical to each other but were found to have nine regions of difference in the genomic sequence when compared to the published reference SCHU S4 sequence. Given the genetic differences and decreased virulence, NR-643/FTS-635 should be clearly designated as a separate SCHU S4 substrain and no longer utilized in efficacy studies to evaluate potential vaccines and therapeutics against tularemia. View Full-Text

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID); National Institute of Allergy and Infectious Diseases (NIAID); Department of Health and Human Services

Grant/Contract Number:: AC02-06CH11357; HHSN272201000037I-HHSN27200001; HHSN272201400027C; U01 AI077909-01; 1 R01 AI123129-01

OSTI ID:: 1787299

Journal Information:: Pathogens, Vol. 10, Issue 6; ISSN 2076-0817

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

References (41)

Comparison of experimental respiratory tularemia in three nonhuman primate species Glynn, Audrey R.; Alves, Derron A.; Frick, Ondraya Comparative Immunology, Microbiology and Infectious Diseases, Vol. 39 https://doi.org/10.1016/j.cimid.2015.01.003	journal	April 2015
AEROSOL INFECTION OF MAN WITH PASTEURELLA TULARENSIS McCrumb, Fred R. Bacteriological Reviews, Vol. 25, Issue 3 https://doi.org/10.1128/BR.25.3.262-267.1961	journal	September 1961
Using MUMmer to Identify Similar Regions in Large Sequence Sets Delcher, Arthur L.; Salzberg, Steven L.; Phillippy, Adam M. Current Protocols in Bioinformatics, Vol. 00, Issue 1 https://doi.org/10.1002/0471250953.bi1003s00	journal	January 2003
Tularemia as a Biological Weapon: Medical and Public Health Management Dennis, David T.; Inglesby, Thomas V.; Henderson, Donald A. JAMA, Vol. 285, Issue 21 https://doi.org/10.1001/jama.285.21.2763	journal	June 2001
Tularemic Pneumonia: Review of American Literature and Report of 15 Additional Cases Stuart, Byron M.; Pullen, Roscoe L. The American Journal of the Medical Sciences, Vol. 210, Issue 2 https://doi.org/10.1097/00000441-194508000-00013	journal	January 1945
SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing Bankevich, Anton; Nurk, Sergey; Antipov, Dmitry Journal of Computational Biology, Vol. 19, Issue 5 https://doi.org/10.1089/cmb.2012.0021	journal	May 2012
Role of Pathogenicity Determinant Protein C (PdpC) in Determining the Virulence of the Francisella tularensis Subspecies tularensis SCHU Uda, Akihiko; Sekizuka, Tsuyoshi; Tanabayashi, Kiyoshi PLoS ONE, Vol. 9, Issue 2 https://doi.org/10.1371/journal.pone.0089075	journal	February 2014
Virulence comparison in mice of distinct isolates of type A Francisella tularensis Twine, Susan M.; Shen, Hua; Kelly, John F. Microbial Pathogenesis, Vol. 40, Issue 3 https://doi.org/10.1016/j.micpath.2005.12.004	journal	March 2006
LIVE TULAREMIA VACCINE I: Host-Parasite Relationship in Monkeys Vaccinated Intracutaneously or Aerogenically Eigelsbach, H. T.; Tulis, J. J.; McGavran, M. H. Journal of Bacteriology, Vol. 84, Issue 5 https://doi.org/10.1128/JB.84.5.1020-1027.1962	journal	November 1962
The complete genome sequence of Francisella tularensis, the causative agent of tularemia Larsson, Pär; Oyston, Petra C. F.; Chain, Patrick Nature Genetics, Vol. 37, Issue 2 https://doi.org/10.1038/ng1499	journal	January 2005
Pneumonic Tularemia in Rabbits Resembles the Human Disease as Illustrated by Radiographic and Hematological Changes after Infection Reed, Douglas S.; Smith, Le'Kneitah; Dunsmore, Tammy PLoS ONE, Vol. 6, Issue 9 https://doi.org/10.1371/journal.pone.0024654	journal	September 2011
Identification of Mechanisms for Attenuation of the FSC043 Mutant of Francisella tularensis SCHU S4 Lindgren, Marie; Tancred, Linda; Golovliov, Igor Infection and Immunity, Vol. 82, Issue 9 https://doi.org/10.1128/IAI.01406-13	journal	September 2014
Fast gapped-read alignment with Bowtie 2 Langmead, Ben; Salzberg, Steven L. Nature Methods, Vol. 9, Issue 4 https://doi.org/10.1038/nmeth.1923	journal	March 2012
The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4 Hutt, Julie A.; Lovchik, Julie A.; Dekonenko, Alexander The American Journal of Pathology, Vol. 187, Issue 2 https://doi.org/10.1016/j.ajpath.2016.09.021	journal	February 2017
Inactivation of vegetative bacterial threat agents on environmental surfaces Calfee, M. Worth; Wendling, Morgan Science of The Total Environment, Vol. 443 https://doi.org/10.1016/j.scitotenv.2012.11.002	journal	January 2013
High-quality draft assemblies of mammalian genomes from massively parallel sequence data Gnerre, S.; MacCallum, I.; Przybylski, D. Proceedings of the National Academy of Sciences, Vol. 108, Issue 4 https://doi.org/10.1073/pnas.1017351108	journal	December 2010
BLAST+: architecture and applications Camacho, Christiam; Coulouris, George; Avagyan, Vahram BMC Bioinformatics, Vol. 10, Issue 1 https://doi.org/10.1186/1471-2105-10-421	journal	January 2009
Improvements to PATRIC, the all-bacterial Bioinformatics Database and Analysis Resource Center Wattam, Alice R.; Davis, James J.; Assaf, Rida Nucleic Acids Research, Vol. 45, Issue D1 https://doi.org/10.1093/nar/gkw1017	journal	November 2016
Unipro UGENE: a unified bioinformatics toolkit Okonechnikov, Konstantin; Golosova, Olga; Fursov, Mikhail Bioinformatics, Vol. 28, Issue 8 https://doi.org/10.1093/bioinformatics/bts091	journal	February 2012
Live Attenuated Mutants of Francisella tularensis Protect Rabbits against Aerosol Challenge with a Virulent Type A Strain Reed, Douglas S.; Smith, Le'Kneitah P.; Cole, Kelly Stefano Infection and Immunity, Vol. 82, Issue 5 https://doi.org/10.1128/IAI.01498-14	journal	March 2014
Francisella tularensis Subtype A.II Genomic Plasticity in Comparison with Subtype A.I Larson, Marilynn A.; Nalbantoglu, Ufuk; Sayood, Khalid PLOS ONE, Vol. 10, Issue 4 https://doi.org/10.1371/journal.pone.0124906	journal	April 2015
Antibiotic prophylaxis and therapy of airborne tularemia Sawyer, W. D.; Dangerfield, H. G.; Hogge, A. L. Bacteriological Reviews, Vol. 30, Issue 3 https://doi.org/10.1128/BR.30.3.542-550.1966	journal	September 1966
Whole-Genome Sequencing Reveals Distinct Mutational Patterns in Closely Related Laboratory and Naturally Propagated Francisella tularensis Strains Sjödin, Andreas; Svensson, Kerstin; Lindgren, Marie PLoS ONE, Vol. 5, Issue 7 https://doi.org/10.1371/journal.pone.0011556	journal	July 2010
Aerosol prime-boost vaccination provides strong protection in outbred rabbits against virulent type A Francisella tularensis O’Malley, Katherine J.; Bowling, Jennifer L.; Stinson, Elizabeth PLOS ONE, Vol. 13, Issue 10 https://doi.org/10.1371/journal.pone.0205928	journal	October 2018
Pathology of Inhalational Francisella tularensis spp. tularensis SCHU S4 Infection in African Green Monkeys (Chlorocebus aethiops) Twenhafel, N. A.; Alves, D. A.; Purcell, B. K. Veterinary Pathology, Vol. 46, Issue 4 https://doi.org/10.1354/vp.08-VP-0302-T-AM	journal	March 2009
Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model Stinson, Elizabeth; Smith, Le'Kneitah P.; Cole, Kelly Stefano Pathogens and Disease, Vol. 74, Issue 7 https://doi.org/10.1093/femspd/ftw079	journal	August 2016
The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule Guina, Tina; Lanning, Lynda L.; Omland, Kristian S. Frontiers in Cellular and Infection Microbiology, Vol. 8 https://doi.org/10.3389/fcimb.2018.00099	journal	April 2018
Pathogenesis of Experimental Respiratory Tularemia in Monkeys White, J. D.; Rooney, J. R.; Prickett, P. A. Journal of Infectious Diseases, Vol. 114, Issue 3 https://doi.org/10.1093/infdis/114.3.277	journal	June 1964
Studies on the Variation of Bacterium Tularense Eigelsbach, H. T.; Braun, Werner; Herring, Ruth D. Journal of Bacteriology, Vol. 61, Issue 5 https://doi.org/10.1128/JB.61.5.557-569.1951	journal	May 1951
Tularemia Vaccine Study: II. Respiratory Challenge Saslaw, Samuel Archives of Internal Medicine, Vol. 107, Issue 5 https://doi.org/10.1001/archinte.1961.03620050068007	journal	May 1961
Growth conditions and environmental factors impact aerosolization but not virulence of Francisella tularensis infection in mice Faith, Seth A.; Smith, Le'Kneitah P.; Swatland, Angela S. Frontiers in Cellular and Infection Microbiology, Vol. 2 https://doi.org/10.3389/fcimb.2012.00126	journal	January 2012
A Mutant of Francisella tularensis Strain SCHU S4 Lacking the Ability To Express a 58-Kilodalton Protein Is Attenuated for Virulence and Is an Effective Live Vaccine Twine, Susan; Byström, Mona; Chen, Wangxue Infection and Immunity, Vol. 73, Issue 12 https://doi.org/10.1128/IAI.73.12.8345-8352.2005	journal	December 2005
The Sequence Alignment/Map format and SAMtools Li, H.; Handsaker, B.; Wysoker, A. Bioinformatics, Vol. 25, Issue 16 https://doi.org/10.1093/bioinformatics/btp352	journal	June 2009
Respiratory tularemia: comparison of selected routes of vaccination in Fischer 344 rats Jemski, J. V. Infection and Immunity, Vol. 34, Issue 3 https://doi.org/10.1128/IAI.34.3.766-772.1981	journal	December 1981
An Outbreak of Primary Pneumonic Tularemia on Martha's Vineyard Feldman, Katherine A.; Enscore, Russell E.; Lathrop, Sarah L. New England Journal of Medicine, Vol. 345, Issue 22 https://doi.org/10.1056/NEJMoa011374	journal	November 2001
Large Direct Repeats Flank Genomic Rearrangements between a New Clinical Isolate of Francisella tularensis subsp. tularensis A1 and Schu S4 Nalbantoglu, Ufuk; Sayood, Khalid; Dempsey, Michael P. PLoS ONE, Vol. 5, Issue 2 https://doi.org/10.1371/journal.pone.0009007	journal	February 2010
Purification and Biophysical Characterization of the CapA Membrane Protein FTT0807 from Francisella tularensis Martin-Garcia, Jose M.; Hansen, Debra T.; Zook, James Biochemistry, Vol. 53, Issue 12 https://doi.org/10.1021/bi401644s	journal	March 2014
Virulence difference between the prototypic Schu S4 strain (A1a) and Francisella tularensisA1a, A1b, A2 and type B strains in a murine model of infection Molins, Claudia R.; Delorey, Mark J.; Yockey, Brook M. BMC Infectious Diseases, Vol. 14, Issue 1 https://doi.org/10.1186/1471-2334-14-67	journal	February 2014
Best practices for evaluating single nucleotide variant calling methods for microbial genomics Olson, Nathan D.; Lund, Steven P.; Colman, Rebecca E. Frontiers in Genetics, Vol. 6 https://doi.org/10.3389/fgene.2015.00235	journal	July 2015
Aerogenic immunization of man with live Tularemia vaccine Hornick, R. B.; Eigelsbach, H. T. Bacteriological Reviews, Vol. 30, Issue 3 https://doi.org/10.1128/BR.30.3.532-538.1966	journal	September 1966
Development, Characterization, and Standardization of a Nose-Only Inhalation Exposure System for Exposure of Rabbits to Small-Particle Aerosols Containing Francisella tularensis O’Malley, Katherine J.; Bowling, Jennifer D.; Barry, Eileen M. Infection and Immunity, Vol. 87, Issue 8 https://doi.org/10.1128/IAI.00198-19	journal	August 2019

Similar Records

Further Characterization of the Capsule-Like Complex (CLC) Produced by Francisella tularensis Subspecies tularensis: Protective Efficacy and Similarity to Outer Membrane Vesicles

Journal Article · Fri Jun 15 00:00:00 EDT 2018 · Frontiers in Cellular and Infection Microbiology · OSTI ID:1787299

Champion, Anna E.; Bandara, Aloka B.; Mohapatra, Nrusingh; +3 more

Rapid Countermeasure Discovery against Francisella tularensis Based on a Metabolic Network Reconstruction

Journal Article · Tue May 21 00:00:00 EDT 2013 · PLoS ONE · OSTI ID:1787299

Chaudhury, Sidhartha; Abdulhameed, Mohamed Diwan M.; Singh, Narender; +15 more

Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies

Journal Article · Mon Jun 06 00:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America · OSTI ID:1787299

Chen, Linxiao; Valentine, Jenny L.; Huang, Chung-Jr; +14 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Francisella tularensis
SCHU S4
attenuation
rabbits
rats
substrain
virulence

Title: Identification of an Attenuated Substrain of Francisella tularensis SCHU S4 by Phenotypic and Genotypic Analyses

Citation Formats

References (41)

Similar Records

Related Subjects