Tn-Seq reveals hidden complexity in the utilization of host-derived glutathione in Francisella tularensis


Autoři: Kathryn M. Ramsey aff001;  Hannah E. Ledvina aff003;  Tenayaann M. Tresko aff003;  Jamie M. Wandzilak aff002;  Catherine A. Tower aff003;  Thomas Tallo aff001;  Caroline E. Schramm aff004;  S. Brook Peterson aff003;  Shawn J. Skerrett aff004;  Joseph D. Mougous aff003;  Simon L. Dove aff001
Působiště autorů: Division of Infectious Diseases, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America aff001;  Departments of Cell and Molecular Biology and Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island, United States of America aff002;  Department of Microbiology, University of Washington School of Medicine, Seattle, Washington, United States of America aff003;  Division of Pulmonary, Critical Care and Sleep Medicine, Harborview Medical Center, University of Washington, Seattle, Washington, United States of America aff004;  Howard Hughes Medical Institute, University of Washington, Seattle, Washington, United States of America aff005
Vyšlo v časopise: Tn-Seq reveals hidden complexity in the utilization of host-derived glutathione in Francisella tularensis. PLoS Pathog 16(6): e32767. doi:10.1371/journal.ppat.1008566
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008566

Souhrn

Host-derived glutathione (GSH) is an essential source of cysteine for the intracellular pathogen Francisella tularensis. In a comprehensive transposon insertion sequencing screen, we identified several F. tularensis genes that play central and previously unappreciated roles in the utilization of GSH during the growth of the bacterium in macrophages. We show that one of these, a gene we named dptA, encodes a proton-dependent oligopeptide transporter that enables growth of the organism on the dipeptide Cys-Gly, a key breakdown product of GSH generated by the enzyme γ-glutamyltranspeptidase (GGT). Although GGT was thought to be the principal enzyme involved in GSH breakdown in F. tularensis, our screen identified a second enzyme, referred to as ChaC, that is also involved in the utilization of exogenous GSH. However, unlike GGT and DptA, we show that the importance of ChaC in supporting intramacrophage growth extends beyond cysteine acquisition. Taken together, our findings provide a compendium of F. tularensis genes required for intracellular growth and identify new players in the metabolism of GSH that could be attractive targets for therapeutic intervention.

Klíčová slova:

Cysteine – Cytoplasm – Francisella – Francisella tularensis – Genetic screens – Library screening – Macrophages – Transposable elements


Zdroje

1. Kingry LC, Petersen JM. Comparative review of Francisella tularensis and Francisella novicida. Front Cell Infect Microbiol. 2014;4:35. doi: 10.3389/fcimb.2014.00035 24660164; PubMed Central PMCID: PMC3952080.

2. Keim P, Johansson A, Wagner DM. Molecular epidemiology, evolution, and ecology of Francisella. Ann N Y Acad Sci. 2007;1105:30–66. doi: 10.1196/annals.1409.011 17435120.

3. Ellis J, Oyston PC, Green M, Titball RW. Tularemia. Clin Microbiol Rev. 2002;15(4):631–46. Epub 2002/10/05. doi: 10.1128/cmr.15.4.631-646.2002 12364373; PubMed Central PMCID: PMC126859.

4. Llewellyn AC, Jones CL, Napier BA, Bina JE, Weiss DS. Macrophage replication screen identifies a novel Francisella hydroperoxide resistance protein involved in virulence. PLoS One. 2011;6(9):e24201. Epub 2011/09/15. doi: 10.1371/journal.pone.0024201 21915295; PubMed Central PMCID: PMC3167825.

5. Roberts LM, Tuladhar S, Steele SP, Riebe KJ, Chen CJ, Cumming RI, et al. Identification of early interactions between Francisella and the host. Infect Immun. 2014;82(6):2504–10. Epub 2014/04/02. doi: 10.1128/IAI.01654-13 24686053; PubMed Central PMCID: PMC4019147.

6. Nano FE, Zhang N, Cowley SC, Klose KE, Cheung KK, Roberts MJ, et al. A Francisella tularensis pathogenicity island required for intramacrophage growth. J Bacteriol. 2004;186(19):6430–6. doi: 10.1128/JB.186.19.6430-6436.2004 15375123; PubMed Central PMCID: PMC516616.

7. Russell AB, Wexler AG, Harding BN, Whitney JC, Bohn AJ, Goo YA, et al. A type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism. Cell Host Microbe. 2014;16(2):227–36. Epub 2014/07/30. doi: 10.1016/j.chom.2014.07.007 25070807; PubMed Central PMCID: PMC4136423.

8. Eshraghi A, Kim J, Walls AC, Ledvina HE, Miller CN, Ramsey KM, et al. Secreted Effectors Encoded within and outside of the Francisella Pathogenicity Island Promote Intramacrophage Growth. Cell Host Microbe. 2016;20(5):573–83. doi: 10.1016/j.chom.2016.10.008 27832588.

9. Barker JR, Chong A, Wehrly TD, Yu JJ, Rodriguez SA, Liu J, et al. The Francisella tularensis pathogenicity island encodes a secretion system that is required for phagosome escape and virulence. Mol Microbiol. 2009;74(6):1459–70. doi: 10.1111/j.1365-2958.2009.06947.x 20054881; PubMed Central PMCID: PMC2814410.

10. Broms JE, Meyer L, Sun K, Lavander M, Sjostedt A. Unique substrates secreted by the type VI secretion system of Francisella tularensis during intramacrophage infection. PLoS One. 2012;7(11):e50473. doi: 10.1371/journal.pone.0050473 23185631; PubMed Central PMCID: PMC3502320.

11. Meibom KL, Charbit A. Francisella tularensis metabolism and its relation to virulence. Front Microbiol. 2010;1:140. Epub 2010/01/01. doi: 10.3389/fmicb.2010.00140 21687763; PubMed Central PMCID: PMC3109416.

12. Ziveri J, Barel M, Charbit A. Importance of Metabolic Adaptations in Francisella Pathogenesis. Front Cell Infect Microbiol. 2017;7:96. Epub 2017/04/13. doi: 10.3389/fcimb.2017.00096 28401066; PubMed Central PMCID: PMC5368251.

13. Alkhuder K, Meibom KL, Dubail I, Dupuis M, Charbit A. Glutathione provides a source of cysteine essential for intracellular multiplication of Francisella tularensis. PLoS Pathog. 2009;5(1):e1000284. Epub 2009/01/23. doi: 10.1371/journal.ppat.1000284 19158962; PubMed Central PMCID: PMC2629122.

14. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009;30(1–2):1–12. Epub 2008/09/18. doi: 10.1016/j.mam.2008.08.006 18796312; PubMed Central PMCID: PMC2696075.

15. Ireland PM, LeButt H, Thomas RM, Oyston PC. A Francisella tularensis SCHU S4 mutant deficient in gamma-glutamyltransferase activity induces protective immunity: characterization of an attenuated vaccine candidate. Microbiology. 2011;157(Pt 11):3172–9. Epub 2011/08/20. doi: 10.1099/mic.0.052902-0 21852349.

16. Kaur A, Gautam R, Srivastava R, Chandel A, Kumar A, Karthikeyan S, et al. ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione. J Biol Chem. 2017;292(2):638–51. Epub 2016/12/04. doi: 10.1074/jbc.M116.727479 27913623; PubMed Central PMCID: PMC5241738.

17. Kumar A, Tikoo S, Maity S, Sengupta S, Sengupta S, Kaur A, et al. Mammalian proapoptotic factor ChaC1 and its homologues function as gamma-glutamyl cyclotransferases acting specifically on glutathione. EMBO Rep. 2012;13(12):1095–101. Epub 2012/10/17. doi: 10.1038/embor.2012.156 23070364; PubMed Central PMCID: PMC3512401.

18. Mungrue IN, Pagnon J, Kohannim O, Gargalovic PS, Lusis AJ. CHAC1/MGC4504 is a novel proapoptotic component of the unfolded protein response, downstream of the ATF4-ATF3-CHOP cascade. J Immunol. 2009;182(1):466–76. Epub 2008/12/26. doi: 10.4049/jimmunol.182.1.466 19109178; PubMed Central PMCID: PMC2846782.

19. Asare R, Abu Kwaik Y. Molecular complexity orchestrates modulation of phagosome biogenesis and escape to the cytosol of macrophages by Francisella tularensis. Environ Microbiol. 2010;12(9):2559–86. Epub 2010/05/21. doi: 10.1111/j.1462-2920.2010.02229.x 20482590; PubMed Central PMCID: PMC2957515.

20. Asare R, Akimana C, Jones S, Abu Kwaik Y. Molecular bases of proliferation of Francisella tularensis in arthropod vectors. Environ Microbiol. 2010;12(9):2587–612. Epub 2010/05/21. doi: 10.1111/j.1462-2920.2010.02230.x 20482589; PubMed Central PMCID: PMC2957557.

21. 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(8):3015–25. Epub 2015/05/20. doi: 10.1128/IAI.00004-15 25987704; PubMed Central PMCID: PMC4496600.

22. Ireland PM, Bullifent HL, Senior NJ, Southern SJ, Yang ZR, Ireland RE, et al. Global Analysis of Genes Essential for Francisella tularensis Schu S4 Growth In Vitro and for Fitness during Competitive Infection of Fischer 344 Rats. J Bacteriol. 2019;201(7). Epub 2019/01/16. doi: 10.1128/JB.00630-18 30642993; PubMed Central PMCID: PMC6416918.

23. Kraemer PS, Mitchell A, Pelletier MR, Gallagher LA, Wasnick M, Rohmer L, et al. Genome-wide screen in Francisella novicida for genes required for pulmonary and systemic infection in mice. Infect Immun. 2009;77(1):232–44. Epub 2008/10/29. doi: 10.1128/IAI.00978-08 18955478; PubMed Central PMCID: PMC2612238.

24. Lindemann SR, Peng K, Long ME, Hunt JR, Apicella MA, Monack DM, et al. Francisella tularensis Schu S4 O-antigen and capsule biosynthesis gene mutants induce early cell death in human macrophages. Infect Immun. 2011;79(2):581–94. Epub 2010/11/17. doi: 10.1128/IAI.00863-10 21078861; PubMed Central PMCID: PMC3028865.

25. Maier TM, Casey MS, Becker RH, Dorsey CW, Glass EM, Maltsev N, et al. Identification of Francisella tularensis Himar1-based transposon mutants defective for replication in macrophages. Infect Immun. 2007;75(11):5376–89. Epub 2007/08/08. doi: 10.1128/IAI.00238-07 17682043; PubMed Central PMCID: PMC2168294.

26. Moule MG, Monack DM, Schneider DS. Reciprocal analysis of Francisella novicida infections of a Drosophila melanogaster model reveal host-pathogen conflicts mediated by reactive oxygen and imd-regulated innate immune response. PLoS Pathog. 2010;6(8):e1001065. Epub 2010/09/25. doi: 10.1371/journal.ppat.1001065 20865166; PubMed Central PMCID: PMC2928790.

27. Peng K, Monack DM. Indoleamine 2,3-dioxygenase 1 is a lung-specific innate immune defense mechanism that inhibits growth of Francisella tularensis tryptophan auxotrophs. Infect Immun. 2010;78(6):2723–33. Epub 2010/04/14. doi: 10.1128/IAI.00008-10 20385761; PubMed Central PMCID: PMC2876573.

28. Qin A, Mann BJ. Identification of transposon insertion mutants of Francisella tularensis tularensis strain Schu S4 deficient in intracellular replication in the hepatic cell line HepG2. BMC microbiology. 2006;6:69. Epub 2006/08/02. doi: 10.1186/1471-2180-6-69 16879747; PubMed Central PMCID: PMC1557513.

29. Su J, Yang J, Zhao D, Kawula TH, Banas JA, Zhang JR. Genome-wide identification of Francisella tularensis virulence determinants. Infection and immunity. 2007;75(6):3089–101. doi: 10.1128/IAI.01865-06 17420240; PubMed Central PMCID: PMC1932872.

30. Weiss DS, Brotcke A, Henry T, Margolis JJ, Chan K, Monack DM. In vivo negative selection screen identifies genes required for Francisella virulence. Proc Natl Acad Sci U S A. 2007;104(14):6037–42. doi: 10.1073/pnas.0609675104 17389372; PubMed Central PMCID: PMC1832217.

31. Oyston PC, Sjostedt A, Titball RW. Tularaemia: bioterrorism defence renews interest in Francisella tularensis. Nat Rev Microbiol. 2004;2(12):967–78. Epub 2004/11/20. doi: 10.1038/nrmicro1045 15550942.

32. Ozanic M, Marecic V, Lindgren M, Sjostedt A, Santic M. Phenotypic characterization of the Francisella tularensis ΔpdpC and ΔiglG mutants. Microbes Infect. 2016;18(12):768–76. doi: 10.1016/j.micinf.2016.07.006 27477000.

33. Goodman AL, McNulty NP, Zhao Y, Leip D, Mitra RD, Lozupone CA, et al. Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe. 2009; 6(3):279–89. https://doi.org/10.1016/j.chom.2009.08.003 19748469.

34. Charity JC, Blalock LT, Costante-Hamm MM, Kasper DL, Dove SL. Small molecule control of virulence gene expression in Francisella tularensis. PLoS Pathog. 2009;5(10):e1000641. Epub 2009/10/31. doi: 10.1371/journal.ppat.1000641 19876386; PubMed Central PMCID: PMC2763202.

35. Pritchard JR, Chao MC, Abel S, Davis BM, Baranowski C, Zhang YJ, et al. ARTIST: high-resolution genome-wide assessment of fitness using transposon-insertion sequencing. PLoS Genet. 2014;10(11):e1004782. doi: 10.1371/journal.pgen.1004782 25375795; PubMed Central PMCID: PMC4222735.

36. Gesbert G, Ramond E, Rigard M, Frapy E, Dupuis M, Dubail I, et al. Asparagine assimilation is critical for intracellular replication and dissemination of Francisella. Cell Microbiol. 2014;16(3):434–49. Epub 2013/10/19. doi: 10.1111/cmi.12227 24134488.

37. Radlinski LC, Brunton J, Steele S, Taft-Benz S, Kawula TH. Defining the Metabolic Pathways and Host-Derived Carbon Substrates Required for Francisella tularensis Intracellular Growth. mBio. 2018;9(6). Epub 2018/11/22. doi: 10.1128/mBio.01471-18 30459188; PubMed Central PMCID: PMC6247087.

38. Ramond E, Gesbert G, Guerrera IC, Chhuon C, Dupuis M, Rigard M, et al. Importance of host cell arginine uptake in Francisella phagosomal escape and ribosomal protein amounts. Mol Cell Proteomics. 2015;14(4):870–81. Epub 2015/01/27. doi: 10.1074/mcp.M114.044552 25616868; PubMed Central PMCID: PMC4390266.

39. Ramond E, Gesbert G, Rigard M, Dairou J, Dupuis M, Dubail I, et al. Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape. PLoS Pathog. 2014;10(1):e1003893. Epub 2014/01/24. doi: 10.1371/journal.ppat.1003893 24453979; PubMed Central PMCID: PMC3894225.

40. Hanes CS, Hird FJ, Isherwood FA. Enzymic transpeptidation reactions involving gamma-glutamyl peptides and alpha-amino-acyl peptides. The Biochemical journal. 1952;51(1):25–35. Epub 1952/04/01. doi: 10.1042/bj0510025 14944528; PubMed Central PMCID: PMC1197783.

41. Daniel H, Spanier B, Kottra G, Weitz D. From bacteria to man: archaic proton-dependent peptide transporters at work. Physiology (Bethesda). 2006;21:93–102. Epub 2006/03/28. doi: 10.1152/physiol.00054.2005 16565475.

42. Osawa H, Stacey G, Gassmann W. ScOPT1 and AtOPT4 function as proton-coupled oligopeptide transporters with broad but distinct substrate specificities. Biochem J. 2006;393(Pt 1):267–75. Epub 2005/09/10. doi: 10.1042/BJ20050920 16149917; PubMed Central PMCID: PMC1383685.

43. Casagrande F, Harder D, Schenk A, Meury M, Ucurum Z, Engel A, et al. Projection structure of DtpD (YbgH), a prokaryotic member of the peptide transporter family. J Mol Biol. 2009;394(4):708–17. Epub 2009/09/29. doi: 10.1016/j.jmb.2009.09.048 19782088.

44. Solcan N, Kwok J, Fowler PW, Cameron AD, Drew D, Iwata S, et al. Alternating access mechanism in the POT family of oligopeptide transporters. EMBO J. 2012;31(16):3411–21. Epub 2012/06/05. doi: 10.1038/emboj.2012.157 22659829; PubMed Central PMCID: PMC3419923.

45. Bachhawat AK, Yadav S. The glutathione cycle: Glutathione metabolism beyond the gamma-glutamyl cycle. IUBMB Life. 2018;70(7):585–92. Epub 2018/04/19. doi: 10.1002/iub.1756 29667297.

46. Oakley AJ, Coggan M, Board PG. Identification and characterization of gamma-glutamylamine cyclotransferase, an enzyme responsible for gamma-glutamyl-epsilon-lysine catabolism. J Biol Chem. 2010;285(13):9642–8. Epub 2010/01/30. doi: 10.1074/jbc.M109.082099 20110353; PubMed Central PMCID: PMC2843214.

47. Oakley AJ, Yamada T, Liu D, Coggan M, Clark AG, Board PG. The identification and structural characterization of C7orf24 as gamma-glutamyl cyclotransferase. An essential enzyme in the gamma-glutamyl cycle. J Biol Chem. 2008;283(32):22031–42. Epub 2008/06/03. doi: 10.1074/jbc.M803623200 18515354.

48. Fujiwara S, Kawazoe T, Ohnishi K, Kitagawa T, Popa C, Valls M, et al. RipAY, a Plant Pathogen Effector Protein, Exhibits Robust gamma-Glutamyl Cyclotransferase Activity When Stimulated by Eukaryotic Thioredoxins. J Biol Chem. 2016;291(13):6813–30. Epub 2016/01/30. doi: 10.1074/jbc.M115.678953 26823466; PubMed Central PMCID: PMC4807269.

49. Mukaihara T, Hatanaka T, Nakano M, Oda K. Ralstonia solanacearum Type III Effector RipAY Is a Glutathione-Degrading Enzyme That Is Activated by Plant Cytosolic Thioredoxins and Suppresses Plant Immunity. mBio. 2016;7(2):e00359–16. Epub 2016/04/14. doi: 10.1128/mBio.00359-16 27073091; PubMed Central PMCID: PMC4959522.

50. Ren G, Champion MM, Huntley JF. Identification of disulfide bond isomerase substrates reveals bacterial virulence factors. Mol Microbiol. 2014;94(4):926–44. Epub 2014/09/27. doi: 10.1111/mmi.12808 25257164; PubMed Central PMCID: PMC4227921.

51. Kadzhaev K, Zingmark C, Golovliov I, Bolanowski M, Shen H, Conlan W, et al. Identification of genes contributing to the virulence of Francisella tularensis SCHU S4 in a mouse intradermal infection model. PLoS One. 2009;4(5):e5463. Epub 2009/05/09. doi: 10.1371/journal.pone.0005463 19424499; PubMed Central PMCID: PMC2675058.

52. Potter AJ, Trappetti C, Paton JC. Streptococcus pneumoniae uses glutathione to defend against oxidative stress and metal ion toxicity. J Bacteriol. 2012;194(22):6248–54. Epub 2012/09/18. doi: 10.1128/JB.01393-12 22984260; PubMed Central PMCID: PMC3486410.

53. Suzuki H, Koyanagi T, Izuka S, Onishi A, Kumagai H. The yliA, -B, -C, and -D genes of Escherichia coli K-12 encode a novel glutathione importer with an ATP-binding cassette. J Bacteriol. 2005;187(17):5861–7. Epub 2005/08/20. doi: 10.1128/JB.187.17.5861-5867.2005 16109926; PubMed Central PMCID: PMC1196167.

54. Vergauwen B, Van der Meeren R, Dansercoer A, Savvides SN. Delineation of the Pasteurellaceae-specific GbpA-family of glutathione-binding proteins. BMC Biochem. 2011;12:59. Epub 2011/11/18. doi: 10.1186/1471-2091-12-59 22087650; PubMed Central PMCID: PMC3295651.

55. Vorwerk H, Mohr J, Huber C, Wensel O, Schmidt-Hohagen K, Gripp E, et al. Utilization of host-derived cysteine-containing peptides overcomes the restricted sulphur metabolism of Campylobacter jejuni. Mol Microbiol. 2014;93(6):1224–45. Epub 2014/07/31. doi: 10.1111/mmi.12732 25074326.

56. Ganguli D, Kumar C, Bachhawat AK. The alternative pathway of glutathione degradation is mediated by a novel protein complex involving three new genes in Saccharomyces cerevisiae. Genetics. 2007;175(3):1137–51. Epub 2006/12/21. doi: 10.1534/genetics.106.066944 17179087; PubMed Central PMCID: PMC1840075.

57. Kaur H, Ganguli D, Bachhawat AK. Glutathione degradation by the alternative pathway (DUG pathway) in Saccharomyces cerevisiae is initiated by (Dug2p-Dug3p)2 complex, a novel glutamine amidotransferase (GATase) enzyme acting on glutathione. J Biol Chem. 2012;287(12):8920–31. Epub 2012/01/27. doi: 10.1074/jbc.M111.327411 22277648; PubMed Central PMCID: PMC3308760.

58. Wang CK, Yang SC, Hsu SC, Chang FP, Lin YT, Chen SF, et al. CHAC2 is essential for self-renewal and glutathione maintenance in human embryonic stem cells. Free Radic Biol Med. 2017;113:439–51. Epub 2017/10/22. doi: 10.1016/j.freeradbiomed.2017.10.345 29054545.

59. Brown MJ, Russo BC, O'Dee DM, Schmitt DM, Nau GJ. The contribution of the glycine cleavage system to the pathogenesis of Francisella tularensis. Microbes Infect. 2014;16(4):300–9. Epub 2014/01/01. doi: 10.1016/j.micinf.2013.12.003 24374051; PubMed Central PMCID: PMC4089098.

60. Goodman AL, Wu M, Gordon JI. Identifying microbial fitness determinants by insertion sequencing using genome-wide transposon mutant libraries. Nat Protoc. 2011;6(12):1969–80. doi: 10.1038/nprot.2011.417 22094732; PubMed Central PMCID: PMC3310428.

61. Goodman AL, Kallstrom G, Faith JJ, Reyes A, Moore A, Dantas G, et al. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proc Natl Acad Sci U S A. 2011; 108(15):6252–7. https://doi.org/10.1073/pnas.1102938108 21436049; PubMed Central PMCID: PMC3076821.

62. Maier TM, Havig A, Casey M, Nano FE, Frank DW, Zahrt TC. Construction and characterization of a highly efficient Francisella shuttle plasmid. App Environ Microbiol. 2004;70(12):7511–9. Epub 2004/12/03. doi: 10.1128/AEM.70.12.7511-7519.2004 15574954; PubMed Central PMCID: PMC535190.

63. Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnetjournal. 2011;17(1).

64. Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10(3):R25. Epub 2009/03/06. doi: 10.1186/gb-2009-10-3-r25 19261174; PubMed Central PMCID: PMC2690996.

65. Ramsey KM, Osborne ML, Vvedenskaya IO, Su C, Nickels BE, Dove SL. Ubiquitous promoter-localization of essential virulence regulators in Francisella tularensis. PLoS Pathog. 2015;11(4):e1004793. Epub 2015/04/02. doi: 10.1371/journal.ppat.1004793 25830507; PubMed Central PMCID: PMC4382096.

66. Charity JC, Costante-Hamm MM, Balon EL, Boyd DH, Rubin EJ, Dove SL. Twin RNA polymerase-associated proteins control virulence gene expression in Francisella tularensis. PLoS Pathog. 2007;3(6):e84. doi: 10.1371/journal.ppat.0030084 17571921.

67. LoVullo ED, Molins-Schneekloth CR, Schweizer HP, Pavelka MS Jr. Single-copy chromosomal integration systems for Francisella tularensis. Microbiology. 2009;155(Pt 4):1152–63. Epub 2009/04/01. doi: 10.1099/mic.0.022491-0 19332817; PubMed Central PMCID: PMC2895234.

68. Ledvina HE, Kelly KA, Eshraghi A, Plemel RL, Peterson SB, Lee B, et al. A Phosphatidylinositol 3-Kinase Effector Alters Phagosomal Maturation to Promote Intracellular Growth of Francisella. Cell Host Microbe. 2018;24(2):285–95 e8. Epub 2018/07/31. doi: 10.1016/j.chom.2018.07.003 30057173.

69. Walters KA, Olsufka R, Kuestner RE, Wu X, Wang K, Skerrett SJ, et al. Prior infection with Type A Francisella tularensis antagonizes the pulmonary transcriptional response to an aerosolized Toll-like receptor 4 agonist. BMC Genomics. 2015;16:874. Epub 2015/10/30. doi: 10.1186/s12864-015-2022-2 26510639; PubMed Central PMCID: PMC4625460.

70. Chamberlain RE. Evaluation of Live Tularemia Vaccine Prepared in a Chemically Defined Medium. Appl Microbiol. 1965;13:232–5. Epub 1965/03/01. 14325885; PubMed Central PMCID: PMC1058227.

71. Ramsey KM, Dove SL. A response regulator promotes Francisella tularensis intramacrophage growth by repressing an anti-virulence factor. Mol Microbiol. 2016;101(4):688–700. Epub 2016/05/14. doi: 10.1111/mmi.13418 27169554; PubMed Central PMCID: PMC5020902.

72. Mortensen BL, Fuller JR, Taft-Benz S, Collins EJ, Kawula TH. Francisella tularensis RipA protein topology and identification of functional domains. J Bacteriol. 2012;194(6):1474–84. Epub 2012/01/24. doi: 10.1128/JB.06327-11 22267515; PubMed Central PMCID: PMC3294868.


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