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Optical In Vivo Imaging in Tuberculosis Research

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Tuberculosis Host-Pathogen Interactions

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Abstract

Tuberculosis remains one of the greatest challenges to global health, making the development of novel diagnostics and therapeutics for tuberculosis a high priority. However, the unique cause, Mycobacterium tuberculosis, demonstrates a number of characteristics that have hindered progress in tuberculosis research. These challenges include an unusually slow growth rate that makes traditional microbiological methods time consuming, a unique glycolipid-rich cell wall that causes bacterial aggregation and complicates enumeration of bacterial loads, and a highly variable disease progression including both acute and chronic stages of infection that can complicate in vivo studies due to variation between infected animals. One strategy that has proven to be remarkably successful in overcoming these challenges is the application of in vivo optical imaging to the study of M. tuberculosis. This approach allows the progress of an infection to be followed in individual animals over time, enabling researchers to better understand this important pathogen and assay new vaccines, treatments, and diagnostic tests more accurately. In this chapter, we discuss the techniques and tools that have been developed to facilitate application of bioluminescent and fluorescent in vivo imaging to tuberculosis research. We also summarize the progress and potential contributions of real-time imaging to the tuberculosis field. Based on recent progress, optical imaging has the potential to transform the field, leading to more rapid discovery of therapeutics, vaccines and mechanisms of pathogenesis.

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References

  1. Andreu N, Zelmer A, Sampson SL, Ikeh M, Bancroft GJ, Schaible UE, Wiles S, Robertson BD. Rapid in vivo assessment of drug efficacy against Mycobacterium tuberculosis using an improved firefly luciferase. J Antimicrob Chemother. 2013;68:2118–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Andreu N, Zelmer A, Wiles S. Noninvasive biophotonic imaging for studies of infectious disease. FEMS Microbiol Rev. 2011;35:360–94.

    Article  CAS  PubMed  Google Scholar 

  3. Carroll P, Schreuder LJ, Muwanguzi-Karugaba J, Wiles S, Robertson BD, Ripoll J, Ward TH, Bancroft GJ, Schaible UE, Parish T. Sensitive detection of gene expression in mycobacteria under replicating and non-replicating conditions using optimized far-red reporters. PLoS One. 2010;5:e9823.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Hutchens M, Luker GD. Applications of bioluminescence imaging to the study of infectious diseases. Cell Microbiol. 2007;9:2315–22.

    Article  CAS  PubMed  Google Scholar 

  5. Jakobs S, Subramaniam V, Schonle A, Jovin TM, Hell SW. EFGP and DsRed expressing cultures of Escherichia coli imaged by confocal, two-photon and fluorescence lifetime microscopy. FEBS Lett. 2000;479:131–5.

    Article  CAS  PubMed  Google Scholar 

  6. Kim D, Hung CF, Wu TC. Monitoring the trafficking of adoptively transferred antigen- specific CD8-positive T cells in vivo, using noninvasive luminescence imaging. Hum Gene Ther. 2007;18:575–88.

    Article  CAS  PubMed  Google Scholar 

  7. Schweichel D, Steitz J, Tormo D, Gaffal E, Ferrer A, Buchs S, Speuser P, Limmer A, Tuting T. Evaluation of DNA vaccination with recombinant adenoviruses using bioluminescence imaging of antigen expression: impact of application routes and delivery with dendritic cells. J Gene Med. 2006;8:1243–50.

    Article  CAS  PubMed  Google Scholar 

  8. Winnard PT Jr, Kluth JB, Raman V. Noninvasive optical tracking of red fluorescent protein-expressing cancer cells in a model of metastatic breast cancer. Neoplasia. 2006;8:796–806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Earl PL, Americo JL, Cotter CA, Moss B. Comparative live bioluminescence imaging of monkeypox virus dissemination in a wild-derived inbred mouse (Mus musculus castaneus) and outbred African dormouse (Graphiurus kelleni). Virology. 2015;475:150–8.

    Article  CAS  PubMed  Google Scholar 

  10. Evans MS, Chaurette JP, Adams ST Jr, Reddy GR, Paley MA, Aronin N, Prescher JA, Miller SC. A synthetic luciferin improves bioluminescence imaging in live mice. Nat Methods. 2014;11:393–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gross S, Abraham U, Prior JL, Herzog ED, Piwnica-Worms D. Continuous delivery of D-luciferin by implanted micro-osmotic pumps enables true real-time bioluminescence imaging of luciferase activity in vivo. Mol Imaging. 2007;6:121–30.

    Article  CAS  PubMed  Google Scholar 

  12. Hiler DJ, Greenwald ML, Geusz ME. Imaging gene expression in live transgenic mice after providing luciferin in drinking water. Photochem Photobiol Sci. 2006;5:1082–5.

    Article  CAS  PubMed  Google Scholar 

  13. Lee S, Cha EJ, Park K, Lee SY, Hong JK, Sun IC, Kim SY, Choi K, Kwon IC, Kim K, Ahn CH. A near-infrared-fluorescence-quenched gold-nanoparticle imaging probe for in vivo drug screening and protease activity determination. Angew Chem Int Ed Engl. 2008;47:2804–7.

    Article  CAS  PubMed  Google Scholar 

  14. Luker KE, Luker GD. Applications of bioluminescence imaging to antiviral research and therapy: multiple luciferase enzymes and quantitation. Antivir Res. 2008;78:179–87.

    Article  CAS  PubMed  Google Scholar 

  15. Rudin M, Weissleder R. Molecular imaging in drug discovery and development. Nat Rev Drug Discov. 2003;2:123–31.

    Article  CAS  PubMed  Google Scholar 

  16. Baker M. Whole-animal imaging: the whole picture. Nature. 2010;463:977–80.

    Article  CAS  PubMed  Google Scholar 

  17. Weissleder R. A clearer vision for in vivo imaging. Nat Biotechnol. 2001;19:316–7.

    Article  CAS  PubMed  Google Scholar 

  18. Xu T, Close D, Handagama W, Marr E, Sayler G, Ripp S. The expanding toolbox of in vivo bioluminescent imaging. Front Oncol. 2016;6:150.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Avci P, Karimi M, Sadasivam M, Antunes-Melo WC, Carrasco E, Hamblin MR. In-vivo monitoring of infectious diseases in living animals using bioluminescence imaging. Virulence. 2018;9:28–63.

    Article  PubMed  Google Scholar 

  20. Kim JE, Kalimuthu S, Ahn BC. In vivo cell tracking with bioluminescence imaging. Nucl Med Mol Imaging. 2015;49:3–10.

    Article  CAS  PubMed  Google Scholar 

  21. Choy G, Choyke P, Libutti SK. Current advances in molecular imaging: noninvasive in vivo bioluminescent and fluorescent optical imaging in cancer research. Mol Imaging. 2003;2:303–12.

    Article  CAS  PubMed  Google Scholar 

  22. Rao J, Dragulescu-Andrasi A, Yao H. Fluorescence imaging in vivo: recent advances. Curr Opin Biotechnol. 2007;18:17–25.

    Article  CAS  PubMed  Google Scholar 

  23. Scheuer W, van Dam GM, Dobosz M, Schwaiger M, Ntziachristos V. Drug-based optical agents: infiltrating clinics at lower risk. Sci Transl Med. 2012;4:134ps11.

    Article  PubMed  CAS  Google Scholar 

  24. Hoffman RM. Use of fluorescent proteins and color-coded imaging to visualize cancer cells with different genetic properties. Cancer Metastasis Rev. 2016;35:5–19.

    Article  CAS  PubMed  Google Scholar 

  25. Licha K, Olbrich C. Optical imaging in drug discovery and diagnostic applications. Adv Drug Deliv Rev. 2005;57:1087–108.

    Article  CAS  PubMed  Google Scholar 

  26. Andreu N, Fletcher T, Krishnan N, Wiles S, Robertson BD. Rapid measurement of antituberculosis drug activity in vitro and in macrophages using bioluminescence. J Antimicrob Chemother. 2012;67:404–14.

    Article  CAS  PubMed  Google Scholar 

  27. Andreu N, Zelmer A, Fletcher T, Elkington PT, Ward TH, Ripoll J, Parish T, Bancroft GJ, Schaible U, Robertson BD, Wiles S. Optimisation of bioluminescent reporters for use with mycobacteria. PLoS One. 2010;5:e10777.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Kong Y, Yao H, Ren H, Subbian S, Cirillo SL, Sacchettini JC, Rao J, Cirillo JD. Imaging tuberculosis with endogenous beta-lactamase reporter enzyme fluorescence in live mice. Proc Natl Acad Sci U S A. 2010;107:12239–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ollinger J, Bailey MA, Moraski GC, Casey A, Florio S, Alling T, Miller MJ, Parish T. A dual read-out assay to evaluate the potency of compounds active against Mycobacterium tuberculosis. PLoS One. 2013;8:e60531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Singh V, Biswas RK, Singh BN. Double recombinant Mycobacterium bovis BCG strain for screening of primary and rationale-based antimycobacterial compounds. Antimicrob Agents Chemother. 2014;58:1389–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Vocat A, Hartkoorn RC, Lechartier B, Zhang M, Dhar N, Cole ST, Sala C. Bioluminescence for assessing drug potency against nonreplicating Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2015;59:4012–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zelmer A, Carroll P, Andreu N, Hagens K, Mahlo J, Redinger N, Robertson BD, Wiles S, Ward TH, Parish T, Ripoll J, Bancroft GJ, Schaible UE. A new in vivo model to test anti-tuberculosis drugs using fluorescence imaging. J Antimicrob Chemother. 2012;67:1948–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhang T, Li SY, Nuermberger EL. Autoluminescent Mycobacterium tuberculosis for rapid, real-time, non-invasive assessment of drug and vaccine efficacy. PLoS One. 2012;7:e29774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Passamaneck YJ, Di Gregorio A, Papaioannou VE, Hadjantonakis AK. Live imaging of fluorescent proteins in chordate embryos: from ascidians to mice. Microsc Res Tech. 2006;69:160–7.

    Article  PubMed  Google Scholar 

  35. Wacker SA, Oswald F, Wiedenmann J, Knochel W. A green to red photoconvertible protein as an analyzing tool for early vertebrate development. Dev Dyn. 2007;236:473–80.

    Article  CAS  PubMed  Google Scholar 

  36. Benard EL, van der Sar AM, Ellett F, Lieschke GJ, Spaink HP, Meijer AH. Infection of zebrafish embryos with intracellular bacterial pathogens. J Vis Exp. 2012;(61):e3781. https://doi.org/10.3791/3781.

  37. Davis JM, Clay H, Lewis JL, Ghori N, Herbomel P, Ramakrishnan L. Real-time visualization of mycobacterium-macrophage interactions leading to initiation of granuloma formation in zebrafish embryos. Immunity. 2002;17:693–702.

    Article  CAS  PubMed  Google Scholar 

  38. van der Sar AM, Musters RJ, van Eeden FJ, Appelmelk BJ, Vandenbroucke-Grauls CM, Bitter W. Zebrafish embryos as a model host for the real time analysis of Salmonella typhimurium infections. Cell Microbiol. 2003;5:601–11.

    Google Scholar 

  39. Hoffman RM. Advantages of multi-color fluorescent proteins for whole-body and in vivo cellular imaging. J Biomed Opt. 2005;10:41202.

    Article  PubMed  CAS  Google Scholar 

  40. Seitz G, Warmann SW, Fuchs J, Mau-Holzmann UA, Ruck P, Heitmann H, Hoffman RM, Mahrt J, Muller GA, Wessels JT. Visualization of xenotransplanted human rhabdomyosarcoma after transfection with red fluorescent protein. J Pediatr Surg. 2006;41:1369–76.

    Article  PubMed  Google Scholar 

  41. Shcherbo D, Merzlyak EM, Chepurnykh TV, Fradkov AF, Ermakova GV, Solovieva EA, Lukyanov KA, Bogdanova EA, Zaraisky AG, Lukyanov S, Chudakov DM. Bright far-red fluorescent protein for whole-body imaging. Nat Methods. 2007;4:741–6.

    Article  CAS  PubMed  Google Scholar 

  42. Stewart CN Jr. Go with the glow: fluorescent proteins to light transgenic organisms. Trends Biotechnol. 2006;24:155–62.

    Article  CAS  PubMed  Google Scholar 

  43. Muller-Taubenberger A, Anderson KI. Recent advances using green and red fluorescent protein variants. Appl Microbiol Biotechnol. 2007;77:1–12.

    Article  PubMed  CAS  Google Scholar 

  44. Shaner NC, Steinbach PA, Tsien RY. A guide to choosing fluorescent proteins. Nat Methods. 2005;2:905–9.

    Article  CAS  PubMed  Google Scholar 

  45. Kong Y, Yang D, Cirillo SL, Li S, Akin A, Francis KP, Maloney T, Cirillo JD. Application of fluorescent protein expressing strains to evaluation of anti-tuberculosis therapeutic efficacy in vitro and in vivo. PLoS One. 2016;11:e0149972.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Glickman MS, Jacobs WR Jr. Microbial pathogenesis of Mycobacterium tuberculosis: dawn of a discipline. Cell. 2001;104:477–85.

    Article  CAS  PubMed  Google Scholar 

  47. Smith I. Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin Microbiol Rev. 2003;16:463–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zumla A, Raviglione M, Hafner R, Von Reyn CF. Tuberculosis. N Engl J Med. 2013;368:745–55.

    Article  CAS  PubMed  Google Scholar 

  49. Kong Y, Akin AR, Francis KP, Zhang N, Troy TL, Xie H, Rao J, Cirillo SL, Cirillo JD. Whole-body imaging of infection using fluorescence. Curr Protoc Microbiol. 2011;Chapter 2:Unit 2C.3.

    PubMed  Google Scholar 

  50. Wilson T, Hastings JW. Bioluminescence. Annu Rev Cell Dev Biol. 1998;14:197–230.

    Article  CAS  PubMed  Google Scholar 

  51. Meighen EA. Molecular biology of bacterial bioluminescence. Microbiol Rev. 1991;55:123–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Hastings JW, Weber K, Friedland J, Eberhard A, Mitchell GW, Gunsalus A. Structurally distinct bacterial luciferases. Biochemistry. 1969;8:4681–9.

    Article  CAS  PubMed  Google Scholar 

  53. Contag CH, Contag PR, Mullins JI, Spilman SD, Stevenson DK, Benaron DA. Photonic detection of bacterial pathogens in living hosts. Mol Microbiol. 1995;18:593–603.

    Article  CAS  PubMed  Google Scholar 

  54. Francis KP, Joh D, Bellinger-Kawahara C, Hawkinson MJ, Purchio TF, Contag PR. Monitoring bioluminescent Staphylococcus aureus infections in living mice using a novel luxABCDE construct. Infect Immun. 2000;68:3594–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Francis KP, Yu J, Bellinger-Kawahara C, Joh D, Hawkinson MJ, Xiao G, Purchio TF, Caparon MG, Lipsitch M, Contag PR. Visualizing pneumococcal infections in the lungs of live mice using bioluminescent Streptococcus pneumoniae transformed with a novel gram-positive lux transposon. Infect Immun. 2001;69:3350–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lorenz WW, Mccann RO, Longiaru M, Cormier MJ. Isolation and expression of a cDNA encoding Renilla reniformis luciferase. Proc Natl Acad Sci U S A. 1991;88:4438–42.

    Article  CAS  Google Scholar 

  57. de Wet JR, Wood KV, Helinski DR, Deluca M. Cloning of firefly luciferase cDNA and the expression of active luciferase in Escherichia coli. Proc Natl Acad Sci U S A. 1985;82:7870–3.

    Google Scholar 

  58. Wood KV, Lam YA, Mcelroy WD. Introduction to beetle luciferases and their applications. J Biolumin Chemilumin. 1989;4:289–301.

    Article  CAS  PubMed  Google Scholar 

  59. Rice BW, Cable MD, Nelson MB. In vivo imaging of light-emitting probes. J Biomed Opt. 2001;6:432–40.

    Article  CAS  PubMed  Google Scholar 

  60. Zhao H, Doyle TC, Coquoz O, Kalish F, Rice BW, Contag CH. Emission spectra of bioluminescent reporters and interaction with mammalian tissue determine the sensitivity of detection in vivo. J Biomed Opt. 2005;10:41210.

    Article  PubMed  CAS  Google Scholar 

  61. Troy T, Jekic-Mcmullen D, Sambucetti L, Rice B. Quantitative comparison of the sensitivity of detection of fluorescent and bioluminescent reporters in animal models. Mol Imaging. 2004;3:9–23.

    Article  CAS  PubMed  Google Scholar 

  62. Chang M, Anttonen KP, Cirillo SL, Francis KP, Cirillo JD. Real-time bioluminescence imaging of mixed mycobacterial infections. PLoS One. 2014;9:e108341.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Flores AR, Parsons LM, Pavelka MS, Jr. Genetic analysis of the beta-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to beta-lactam antibiotics. Microbiology. 2005;151:521–32.

    Article  CAS  PubMed  Google Scholar 

  64. Hugonnet JE, Blanchard JS. Irreversible inhibition of the Mycobacterium tuberculosis beta-lactamase by clavulanate. Biochemistry. 2007;46:11998–2004.

    Article  CAS  PubMed  Google Scholar 

  65. Ioerger TR, Feng Y, Chen X, Dobos KM, Victor TC, Streicher EM, Warren RM, van Pittius NCG, van Helden PD, Sacchettini JC. The non-clonality of drug resistance in Beijing-genotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africa. BMC Genomics. 2010;11:670.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Voladri RK, Lakey DL, Hennigan SH, Menzies BE, Edwards KM, Kernodle DS. Recombinant expression and characterization of the major beta-lactamase of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1998;42:1375–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zlokarnik G, Negulescu PA, Knapp TE, Mere L, Burres N, Feng L, Whitney M, Roemer K, Tsien RY. Quantitation of transcription and clonal selection of single living cells with beta-lactamase as reporter. Science. 1998;279:84–8.

    Article  CAS  PubMed  Google Scholar 

  68. Kong Y, Cirillo JD. Reporter enzyme fluorescence (REF) imaging and quantification of tuberculosis in live animals. Virulence. 2010;1:558–62.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Yang HJ, Kong Y, Cheng Y, Janagama H, Hassounah H, Xie H, Rao J, Cirillo JD. Real-time imaging of Mycobacterium tuberculosis, using a novel near-infrared fluorescent substrate. J Infect Dis. 2017;215:405–14.

    Google Scholar 

  70. Xing B, Khanamiryan A, Rao J. Cell-permeable near-infrared fluorogenic substrates for imaging beta-lactamase activity. J Am Chem Soc. 2005;127:4158–9.

    Article  CAS  PubMed  Google Scholar 

  71. Siragusa GR, Nawotka K, Spilman SD, Contag PR, Contag CH. Real-time monitoring of Escherichia coli O157:H7 adherence to beef carcass surface tissues with a bioluminescent reporter. Appl Environ Microbiol. 1999;65:1738–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Wiles S, Pickard KM, Peng K, Macdonald TT, Frankel G. In vivo bioluminescence imaging of the murine pathogen Citrobacter rodentium. Infect Immun. 2006;74:5391–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Xiong YQ, Willard J, Kadurugamuwa JL, Yu J, Francis KP, Bayer AS. Real-time in vivo bioluminescent imaging for evaluating the efficacy of antibiotics in a rat Staphylococcus aureus endocarditis model. Antimicrob Agents Chemother. 2005;49:380–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lagendijk EL, Validov S, Lamers GE, De Weert S, Bloemberg GV. Genetic tools for tagging gram-negative bacteria with mCherry for visualization in vitro and in natural habitats, biofilm and pathogenicity studies. FEMS Microbiol Lett. 2010;305:81–90.

    Article  CAS  PubMed  Google Scholar 

  75. Lee J, Attila C, Cirillo SL, Cirillo JD, Wood TK. Indole and 7-hydroxyindole diminish Pseudomonas aeruginosa virulence. Microb Biotechnol. 2009;2:75–90.

    Article  CAS  PubMed  Google Scholar 

  76. Wang X, Li Z, Li B, Chi H, Li J, Fan H, Yao R, Li Q, Dong X, Chen M, Qu H, et al. Bioluminescence imaging of colonization and clearance dynamics of Brucella Suis vaccine strain S2 in mice and guinea pigs. Mol Imaging Biol. 2016;18:519–26.

    Article  CAS  PubMed  Google Scholar 

  77. Chen CH, Durand E, Wang J, Zon LI, Poss KD. Zebraflash transgenic lines for in vivo bioluminescence imaging of stem cells and regeneration in adult zebrafish. Development. 2013;140:4988–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Liang MR, Alestrom P, Collas P. Glowing zebrafish: integration, transmission, and expression of a single luciferase transgene promoted by noncovalent DNA-nuclear transport peptide complexes. Mol Reprod Dev. 2000;55:8–13.

    Article  CAS  PubMed  Google Scholar 

  79. Mayerhofer R, Araki K, Szalay AA. Monitoring of spatial expression of firefly luciferase in transformed zebrafish. J Biolumin Chemilumin. 1995;10:271–5.

    Article  CAS  PubMed  Google Scholar 

  80. Weger M, Weger BD, Diotel N, Rastegar S, Hirota T, Kay SA, Strahle U, Dickmeis T. Real-time in vivo monitoring of circadian E-box enhancer activity: a robust and sensitive zebrafish reporter line for developmental, chemical and neural biology of the circadian clock. Dev Biol. 2013;380:259–73.

    Article  CAS  PubMed  Google Scholar 

  81. Karlsson EA, Meliopoulos VA, Savage C, Livingston B, Mehle A, Schultz-Cherry S. Visualizing real-time influenza virus infection, transmission and protection in ferrets. Nat Commun. 2015;6:6378.

    Article  CAS  PubMed  Google Scholar 

  82. Galbadage T, Shepherd TF, Cirillo SL, Gumienny TL, Cirillo JD. The Caenorhabditis elegans p38 MAPK gene plays a key role in protection from mycobacteria. Microbiology. 2016;5:436–52.

    CAS  Google Scholar 

  83. Galbadage T, Hartman PS. Repeated temperature fluctuation extends the life span of Caenorhabditis elegans in a daf-16-dependent fashion. Mech Ageing Dev. 2008;129:507–14.

    Article  CAS  PubMed  Google Scholar 

  84. Tarantal AF, Lee CC. Long-term luciferase expression monitored by bioluminescence imaging after adeno-associated virus-mediated fetal gene delivery in rhesus monkeys (Macaca mulatta). Hum Gene Ther. 2010;21:143–8.

    Article  CAS  PubMed  Google Scholar 

  85. Tarantal AF, Lee CC, Jimenez DF, Cherry SR. Fetal gene transfer using lentiviral vectors: in vivo detection of gene expression by microPET and optical imaging in fetal and infant monkeys. Hum Gene Ther. 2006;17:1254–61.

    Article  CAS  PubMed  Google Scholar 

  86. Greives MR, Aldrich MB, Sevick-Muraca EM, Rasmussen JC. Near-infrared fluorescence lymphatic imaging of a toddler with congenital lymphedema. Pediatrics. 2017;139:e20154456.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Marshall MV, Rasmussen JC, Tan IC, Aldrich MB, Adams KE, Wang X, Fife CE, Maus EA, Smith LA, Sevick-Muraca EM. Near-infrared fluorescence imaging in humans with indocyanine green: a review and update. Open Surg Oncol J. 2010;2:12–25.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Corlu A, Choe R, Durduran T, Rosen MA, Schweiger M, Arridge SR, Schnall MD, Yodh AG. Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans. Opt Express. 2007;15:6696–716.

    Article  PubMed  Google Scholar 

  89. Intes X, Ripoll J, Chen Y, Nioka S, Yodh AG, Chance B. In vivo continuous-wave optical breast imaging enhanced with Indocyanine Green. Med Phys. 2003;30:1039–47.

    Article  PubMed  Google Scholar 

  90. Piper SK, Habermehl C, Schmitz CH, Kuebler WM, Obrig H, Steinbrink J, Mehnert J. Towards whole-body fluorescence imaging in humans. PLoS One. 2013;8:e83749.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Verjans JW, Jaffer FA. Biological imaging of atherosclerosis: moving beyond anatomy. J Cardiovasc Transl Res. 2013;6:681–94.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Mezzanotte L, An N, Mol IM, Löwik CW, Kaijzel EL. A new multicolor bioluminescence imaging platform to investigate NF-kappaB activity and apoptosis in human breast cancer cells. PLoS One. 2014;9:e85550.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Subach FV, Verkhusha VV. Chromophore transformations in red fluorescent proteins. Chem Rev. 2012;112:4308–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Tomosugi W, Matsuda T, Tani T, Nemoto T, Kotera I, Saito K, Horikawa K, Nagai T. An ultramarine fluorescent protein with increased photostability and pH insensitivity. Nat Methods. 2009;6:351–3.

    Article  CAS  PubMed  Google Scholar 

  95. Rizzo MA, Springer GH, Granada B, Piston DW. An improved cyan fluorescent protein variant useful for FRET. Nat Biotechnol. 2004;22:445–9.

    Article  CAS  PubMed  Google Scholar 

  96. Kremers GJ, Goedhart J, van Munster EB, Gadella TW Jr. Cyan and yellow super fluorescent proteins with improved brightness, protein folding, and FRET Forster radius. Biochemistry. 2006;45:6570–80.

    Article  CAS  PubMed  Google Scholar 

  97. Goedhart J, Van Weeren L, Hink MA, Vischer NO, Jalink K, Gadella TW Jr. Bright cyan fluorescent protein variants identified by fluorescence lifetime screening. Nat Methods. 2010;7:137–9.

    Article  CAS  PubMed  Google Scholar 

  98. Griesbeck O, Baird GS, Campbell RE, Zacharias DA, Tsien RY. Reducing the environmental sensitivity of yellow fluorescent protein. Mechanism and applications. J Biol Chem. 2001;276:29188–94.

    Article  CAS  PubMed  Google Scholar 

  99. Nagai T, Ibata K, Park ES, Kubota M, Mikoshiba K, Miyawaki A. A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications. Nat Biotechnol. 2002;20:87–90.

    Article  CAS  PubMed  Google Scholar 

  100. Cubitt AB, Woollenweber LA, Heim R. Understanding structure-function relationships in the Aequorea victoria green fluorescent protein. Methods Cell Biol. 1999;58:19–30.

    Article  CAS  PubMed  Google Scholar 

  101. Shcherbo D, Souslova EA, Goedhart J, Chepurnykh TV, Gaintzeva A, Shemiakina II, Gadella TW, Lukyanov S, Chudakov DM. Practical and reliable FRET/FLIM pair of fluorescent proteins. BMC Biotechnol. 2009b;9:24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Karasawa S, Araki T, Nagai T, Mizuno H, Miyawaki A. Cyan-emitting and orange-emitting fluorescent proteins as a donor/acceptor pair for fluorescence resonance energy transfer. Biochem J. 2004;381:307–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wang L, Jackson WC, Steinbach PA, Tsien RY. Evolution of new nonantibody proteins via iterative somatic hypermutation. Proc Natl Acad Sci U S A. 2004;101:16745–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Shcherbo D, Murphy CS, Ermakova GV, Solovieva EA, Chepurnykh TV, Shcheglov AS, Verkhusha VV, Pletnev VZ, Hazelwood KL, Roche PM, Lukyanov S, Zaraisky AG, Davidson MW, Chudakov DM. Far-red fluorescent tags for protein imaging in living tissues. Biochem J. 2009a;418:567–74.

    Article  CAS  PubMed  Google Scholar 

  105. Lin MZ, Mckeown MR, Ng HL, Aguilera TA, Shaner NC, Campbell RE, Adams SR, Gross LA, Ma W, Alber T, Tsien RY. Autofluorescent proteins with excitation in the optical window for intravital imaging in mammals. Chem Biol. 2009;16:1169–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Kogure T, Karasawa S, Araki T, Saito K, Kinjo M, Miyawaki A. A fluorescent variant of a protein from the stony coral Montipora facilitates dual-color single-laser fluorescence cross-correlation spectroscopy. Nat Biotechnol. 2006;24:577–81.

    Article  CAS  PubMed  Google Scholar 

  107. Volkman HE, Pozos TC, Zheng J, Davis JM, Rawls JF, Ramakrishnan L. Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium. Science. 2010;327:466–9.

    Article  CAS  PubMed  Google Scholar 

  108. Cosma CL, Humbert O, Ramakrishnan L. Superinfecting mycobacteria home to established tuberculous granulomas. Nat Immunol. 2004;5:828–35.

    Article  CAS  PubMed  Google Scholar 

  109. Tobin DM, Vary JC Jr, Ray JP, Walsh GS, Dunstan SJ, Bang ND, Hagge DA, Khadge S, King MC, Hawn TR, Moens CB. The lta4h locus modulates susceptibility to mycobacterial infection in zebrafish and humans. Cell. 2010;140:717–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Volkman HE, Clay H, Beery D, Chang JC, Sherman DR, Ramakrishnan L. Tuberculous granuloma formation is enhanced by a mycobacterium virulence determinant. PLoS Biol. 2004;2:e367.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Clay H, Davis JM, Beery D, Huttenlocher A, Lyons SE, Ramakrishnan L. Dichotomous role of the macrophage in early Mycobacterium marinum infection of the zebrafish. Cell Host Microbe. 2007;2:29–39.

    Article  CAS  Google Scholar 

  112. Yang CT, Cambier CJ, Davis JM, Hall CJ, Crosier PS, Ramakrishnan L. Neutrophils exert protection in the early tuberculous granuloma by oxidative killing of mycobacteria phagocytosed from infected macrophages. Cell Host Microbe. 2012;12:301–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Berg RD, Levitte S, O’sullivan MP, O’leary SM, Cambier CJ, Cameron J, Takaki KK, Moens CB, Tobin DM, Keane J, Ramakrishnan L. Lysosomal disorders drive susceptibility to tuberculosis by compromising macrophage migration. Cell. 2016;165:139–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Bernut A, Nguyen-Chi M, Halloum I, Herrmann JL, Lutfalla G, Kremer L. Mycobacterium abscessus-induced granuloma formation is strictly dependent on TNF signaling and neutrophil trafficking. PLoS Pathog. 2016;12:e1005986.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Boot M, Jim KK, Liu T, Commandeur S, Lu P, Verboom T, Lill H, Bitter W, Bald D. A fluorescence-based reporter for monitoring expression of mycobacterial cytochrome bd in response to antibacterials and during infection. Sci Rep. 2017;7:10665.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Levitte S, Adams KN, Berg RD, Cosma CL, Urdahl KB, Ramakrishnan L. Mycobacterial acid tolerance enables phagolysosomal survival and establishment of tuberculous infection in vivo. Cell Host Microbe. 2016;20:250–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Smith AM, Mancini MC, Nie S. Bioimaging: second window for in vivo imaging. Nat Nanotechnol. 2009;4:710–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Pansare V, Hejazi S, Faenza W, Prud’homme RK. Review of long-wavelength optical and NIR imaging materials: contrast agents, fluorophores and multifunctional nano carriers. Chem Mater. 2012;24:812–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Heim R, Tsien RY. Engineering green fluorescent protein for improved brightness, longer wavelengths and fluorescence resonance energy transfer. Curr Biol. 1996;6:178–82.

    Article  CAS  PubMed  Google Scholar 

  120. Miyawaki A, Llopis J, Heim R, Mccaffery JM, Adams JA, Ikura M, Tsien RY. Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature. 1997;388:882–7.

    Article  CAS  PubMed  Google Scholar 

  121. Romoser VA, Hinkle PM, Persechini A. Detection in living cells of Ca2+−dependent changes in the fluorescence emission of an indicator composed of two green fluorescent protein variants linked by a calmodulin-binding sequence. A new class of fluorescent indicators. J Biol Chem. 1997;272:13270–4.

    Article  CAS  PubMed  Google Scholar 

  122. Seksek O, Biwersi J, Verkman AS. Direct measurement of trans-Golgi pH in living cells and regulation by second messengers. J Biol Chem. 1995;270:4967–70.

    Article  CAS  PubMed  Google Scholar 

  123. Lippincott-Schwartz J, Snapp E, Kenworthy A. Studying protein dynamics in living cells. Nat Rev Mol Cell Biol. 2001;2:444–56.

    Article  CAS  PubMed  Google Scholar 

  124. Nehls S, Snapp EL, Cole NB, Zaal KJ, Kenworthy AK, Roberts TH, Ellenberg J, Presley JF, Siggia E, Lippincott-Schwartz J. Dynamics and retention of misfolded proteins in native ER membranes. Nat Cell Biol. 2000;2:288–95.

    Article  CAS  PubMed  Google Scholar 

  125. Heim R, Prasher DC, Tsien RY. Wavelength mutations and posttranslational autoxidation of green fluorescent protein. Proc Natl Acad Sci U S A. 1994;91:12501–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Prendergast FG. Biophysics of the green fluorescent protein. Methods Cell Biol. 1999;58:1–18.

    CAS  PubMed  Google Scholar 

  127. Baird GS, Zacharias DA, Tsien RY. Biochemistry, mutagenesis, and oligomerization of DsRed, a red fluorescent protein from coral. Proc Natl Acad Sci U S A. 2000;97:11984–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Bevis BJ, Glick BS. Rapidly maturing variants of the discosoma red fluorescent protein (DsRed). Nat Biotechnol. 2002;20:83–7.

    Article  CAS  PubMed  Google Scholar 

  129. Terskikh A, Fradkov A, Ermakova G, Zaraisky A, Tan P, Kajava AV, Zhao X, Lukyanov S, Matz M, Kim S, Weissman I, Siebert P. “Fluorescent timer”: protein that changes color with time. Science. 2000;290:1585–8.

    Article  CAS  PubMed  Google Scholar 

  130. Yang F, Moss LG, Phillips GN Jr. The molecular structure of green fluorescent protein. Nat Biotechnol. 1996;14:1246–51.

    Article  CAS  PubMed  Google Scholar 

  131. Andresen M, Schmitz-Salue R, Jakobs S. Short tetracysteine tags to beta-tubulin demonstrate the significance of small labels for live cell imaging. Mol Biol Cell. 2004;15:5616–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Davis SJ, Vierstra RD. Soluble, highly fluorescent variants of green fluorescent protein (GFP) for use in higher plants. Plant Mol Biol. 1998;36:521–8.

    Article  CAS  PubMed  Google Scholar 

  133. Sheff MA, Thorn KS. Optimized cassettes for fluorescent protein tagging in Saccharomyces cerevisiae. Yeast. 2004;21:661–70.

    Article  CAS  PubMed  Google Scholar 

  134. Patterson GH, Knobel SM, Sharif WD, Kain SR, Piston DW. Use of the green fluorescent protein and its mutants in quantitative fluorescence microscopy. Biophys J. 1997;73:2782–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Triccas JA, Berthet FX, Pelicic V, Gicquel B. Use of fluorescence induction and sucrose counterselection to identify Mycobacterium tuberculosis genes expressed within host cells. Microbiology. 1999;145(Pt 10):2923–30.

    Article  CAS  PubMed  Google Scholar 

  136. Kong Y, Cirillo JD. Fluorescence imaging of mycobacterial infection in live mice using fluorescent protein-expressing strains. Methods Mol Biol. 2018;1790:75–85.

    Article  CAS  PubMed  Google Scholar 

  137. Sharma S, Gelman E, Narayan C, Bhattacharjee D, Achar V, Humnabadkar V, Balasubramanian V, Ramachandran V, Dhar N, Dinesh N. Simple and rapid method to determine antimycobacterial potency of compounds by using autoluminescent Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2014;58:5801–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Hsiang CY, Hseu YC, Chang YC, Kumar KJ, Ho TY, Yang HL. Toona sinensis and its major bioactive compound gallic acid inhibit LPS-induced inflammation in nuclear factor-kappaB transgenic mice as evaluated by in vivo bioluminescence imaging. Food Chem. 2013;136:426–34.

    Article  CAS  PubMed  Google Scholar 

  139. Maguire CA, Bovenberg MS, Crommentuijn MH, Niers JM, Kerami M, Teng J, Sena-Esteves M, Badr CE, Tannous BA. Triple bioluminescence imaging for in vivo monitoring of cellular processes. Mol Ther Nucleic Acids. 2013;2:e99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Muranaka T, Kubota S, Oyama T. A single-cell bioluminescence imaging system for monitoring cellular gene expression in a plant body. Plant Cell Physiol. 2013;54:2085–93.

    Article  CAS  PubMed  Google Scholar 

  141. Meighen EA. Bacterial bioluminescence: organization, regulation, and application of the lux genes. FASEB J. 1993;7:1016–22.

    Article  CAS  PubMed  Google Scholar 

  142. Baldwin TO. Firefly luciferase: the structure is known, but the mystery remains. Structure. 1996;4:223–8.

    Article  CAS  PubMed  Google Scholar 

  143. Hall MP, Unch J, Binkowski BF, Valley MP, Butler BL, Wood MG, Otto P, Zimmerman K, Vidugiris G, Machleidt T, Robers MB, Benink HA, Eggers CT, Slater MR, Meisenheimer PL, Klaubert DH, Fan F, Encell LP, Wood KV. Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate. ACS Chem Biol. 2012;7:1848–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Heise K, Oppermann H, Meixensberger J, Gebhardt R, Gaunitz F. Dual luciferase assay for secreted luciferases based on Gaussia and NanoLuc. Assay Drug Dev Technol. 2013;11:244–52.

    Article  CAS  PubMed  Google Scholar 

  145. Inouye S, Ohmiya Y, Toya Y, Tsuji FI. Imaging of luciferase secretion from transformed Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1992;89:9584–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Hastings JW, Potrikus CJ, Gupta SC, Kurfurst M, Makemson JC. Biochemistry and physiology of bioluminescent bacteria. Adv Microb Physiol. 1985;26:235–91.

    Article  CAS  PubMed  Google Scholar 

  147. Gahan CG. The bacterial lux reporter system: applications in bacterial localisation studies. Curr Gene Ther. 2012;12:12–9.

    Google Scholar 

  148. Demidova TN, Gad F, Zahra T, Francis KP, Hamblin MR. Monitoring photodynamic therapy of localized infections by bioluminescence imaging of genetically engineered bacteria. J Photochem Photobiol B. 2005;81:15–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Van Staden ADP, Heunis T, Smith C, Deane S, Dicks LM. Efficacy of lantibiotic treatment of Staphylococcus aureus-induced skin infections, monitored by in vivo bioluminescent imaging. Antimicrob Agents Chemother. 2016;60:3948–55.

    Google Scholar 

  150. Dai T, Tegos GP, Zhiyentayev T, Mylonakis E, Hamblin MR. Photodynamic therapy for methicillin-resistant Staphylococcus aureus infection in a mouse skin abrasion model. Lasers Surg Med. 2010;42:38–44.

    Article  PubMed  PubMed Central  Google Scholar 

  151. Vecchio D, Dai T, Huang L, Fantetti L, Roncucci G, Hamblin MR. Antimicrobial photodynamic therapy with RLP068 kills methicillin-resistant Staphylococcus aureus and improves wound healing in a mouse model of infected skin abrasion PDT with RLP068/Cl in infected mouse skin abrasion. J Biophotonics. 2013;6:733–42.

    Article  CAS  PubMed  Google Scholar 

  152. Branchini BR, Southworth TL, Deangelis JP, Roda A, Michelini E. Luciferase from the Italian firefly Luciola italica: molecular cloning and expression. Comp Biochem Physiol B Biochem Mol Biol. 2006;145:159–67.

    Article  CAS  Google Scholar 

  153. Maguire CA, Van Der Mijn JC, Degeling MH, Morse D, Tannous BA. Codon-optimized Luciola italica luciferase variants for mammalian gene expression in culture and in vivo. Mol Imaging. 2012;11:13–21.

    Article  CAS  Google Scholar 

  154. Andrew PW, Roberts IS. Construction of a bioluminescent mycobacterium and its use for assay of antimycobacterial agents. J Clin Microbiol. 1993;31:2251–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Heuts F, Carow B, Wigzell H, Rottenberg ME. Use of non-invasive bioluminescent imaging to assess mycobacterial dissemination in mice, treatment with bactericidal drugs and protective immunity. Microbes Infect. 2009;11:1114–21.

    Article  CAS  PubMed  Google Scholar 

  156. Zhang T, Li SY, Converse PJ, Almeida DV, Grosset JH, Nuermberger EL. Using bioluminescence to monitor treatment response in real time in mice with Mycobacterium ulcerans infection. Antimicrob Agents Chemother. 2011;55:56–61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  157. Hakamata Y, Murakami T, Kobayashi E. “Firefly rats” as an organ/cellular source for long-term in vivo bioluminescent imaging. Transplantation. 2006;81:1179–84.

    Article  PubMed  Google Scholar 

  158. Mcgregor A, Choi KY. Cytomegalovirus antivirals and development of improved animal models. Expert Opin Drug Metab Toxicol. 2011;7:1245–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Moore HA, Whitmore D. Circadian rhythmicity and light sensitivity of the zebrafish brain. PLoS One. 2014;9:e86176.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  160. Kaneko M, Cahill GM. Light-dependent development of circadian gene expression in transgenic zebrafish. PLoS Biol. 2005;3:e34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. Lagido C, Mclaggan D, Flett A, Pettitt J, Glover LA. Rapid sublethal toxicity assessment using bioluminescent Caenorhabditis elegans, a novel whole-animal metabolic biosensor. Toxicol Sci. 2009;109:88–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Tarantal AF, Lee CC, Batchelder CA, Christensen JE, Prater D, Cherry SR. Radiolabeling and in vivo imaging of transplanted renal lineages differentiated from human embryonic stem cells in fetal rhesus monkeys. Mol Imaging Biol. 2012;14:197–204.

    Article  PubMed  PubMed Central  Google Scholar 

  163. Dalton JP, Uy B, Okuda KS, Hall CJ, Denny WA, Crosier PS, Swift S, Wiles S. Screening of anti-mycobacterial compounds in a naturally infected zebrafish larvae model. J Antimicrob Chemother. 2017;72:421–7.

    Article  CAS  PubMed  Google Scholar 

  164. Meighen EA, Dunlap PV. Physiological, biochemical and genetic control of bacterial bioluminescence. Adv Microb Physiol. 1993;34:1–67.

    Article  CAS  PubMed  Google Scholar 

  165. Lee CY, Szittner RB, Meighen EA. The lux genes of the luminous bacterial symbiont, Photobacterium leiognathi, of the ponyfish. Nucleotide sequence, difference in gene organization, and high expression in mutant Escherichia coli. Eur J Biochem. 1991;201:161–7.

    Article  CAS  PubMed  Google Scholar 

  166. Eckstein JW, Cho KW, Colepicolo P, Ghisla S, Hastings JW, Wilson T. A time-dependent bacterial bioluminescence emission spectrum in an in vitro single turnover system: energy transfer alone cannot account for the yellow emission of Vibrio fischeri Y-1. Proc Natl Acad Sci U S A. 1990;87:1466–70.

    Article  CAS  Google Scholar 

  167. O’kane DJ, Prasher DC. Evolutionary origins of bacterial bioluminescence. Mol Microbiol. 1992;6:443–9.

    Article  PubMed  Google Scholar 

  168. Cao JG, Meighen EA. Purification and structural identification of an autoinducer for the luminescence system of Vibrio harveyi. J Biol Chem. 1989;264:21670–6.

    Google Scholar 

  169. Eberhard A, Burlingame AL, Eberhard C, Kenyon GL, Nealson KH, Oppenheimer NJ. Structural identification of autoinducer of Photobacterium fischeri luciferase. Biochemistry. 1981;20:2444–9.

    Article  CAS  PubMed  Google Scholar 

  170. Engebrecht J, Nealson K, Silverman M. Bacterial bioluminescence: isolation and genetic analysis of functions from Vibrio fischeri. Cell. 1983;32:773–81.

    Article  CAS  PubMed  Google Scholar 

  171. Engebrecht J, Silverman M. Identification of genes and gene products necessary for bacterial bioluminescence. Proc Natl Acad Sci U S A. 1984;81:4154–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Rocchetta HL, Boylan CJ, Foley JW, Iversen PW, Letourneau DL, Mcmillian CL, Contag PR, Jenkins DE, Parr TR, Jr. Validation of a noninvasive, real-time imaging technology using bioluminescent Escherichia coli in the neutropenic mouse thigh model of infection. Antimicrob Agents Chemother. 2001;45:129–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Wiles S, Clare S, Harker J, Huett A, Young D, Dougan G, Frankel G. Organ specificity, colonization and clearance dynamics in vivo following oral challenges with the murine pathogen Citrobacter rodentium. Cell Microbiol. 2004;6:963–72.

    Article  CAS  PubMed  Google Scholar 

  174. Hardy J, Francis KP, Deboer M, Chu P, Gibbs K, Contag CH. Extracellular replication of Listeria monocytogenes in the murine gall bladder. Science. 2004;303:851–3.

    Article  CAS  PubMed  Google Scholar 

  175. Sanli G, Blaber SI, Blaber M. Reduction of wobble-position GC bases in Corynebacteria genes and enhancement of PCR and heterologous expression. J Mol Microbiol Biotechnol. 2001;3:123–6.

    CAS  PubMed  Google Scholar 

  176. Craney A, Hohenauer T, Xu Y, Navani NK, Li Y, Nodwell J. A synthetic luxCDABE gene cluster optimized for expression in high-GC bacteria. Nucleic Acids Res. 2007;35:e46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  177. Qazi SN, Counil E, Morrissey J, Rees CE, Cockayne A, Winzer K, Chan WC, Williams P, Hill PJ. agr Expression precedes escape of internalized Staphylococcus aureus from the host endosome. Infect Immun. 2001;69:7074–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Ranes MG, Rauzier J, Lagranderie M, Gheorghiu M, Gicquel B. Functional analysis of pAL5000, a plasmid from Mycobacterium fortuitum: construction of a “mini” mycobacterium-Escherichia coli shuttle vector. J Bacteriol. 1990;172:2793–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Stover CK, de la Cruz VF, Fuerst TR, Burlein JE, Benson LA, Bennett LT, Bansal GP, Young JF, Lee MH, Hatfull GF, et al. New use of BCG for recombinant vaccines. Nature. 1991;351:456–60.

    Article  CAS  PubMed  Google Scholar 

  180. Bourn WR, Jansen Y, Stutz H, Warren RM, Williamson AL, van Helden PD. Creation and characterisation of a high-copy-number version of the pAL5000 mycobacterial replicon. Tuberculosis (Edinb). 2007;87:481–8.

    Article  CAS  Google Scholar 

  181. Baggett B, Roy R, Momen S, Morgan S, Tisi L, Morse D, Gillies RJ. Thermostability of firefly luciferases affects efficiency of detection by in vivo bioluminescence. Mol Imaging. 2004;3:324–32.

    Article  CAS  PubMed  Google Scholar 

  182. Gupta RK, Patterson SS, Ripp S, Simpson ML, Sayler GS. Expression of the Photorhabdus luminescens lux genes (luxA, B, C, D, and E) in Saccharomyces cerevisiae. FEMS Yeast Res. 2003;4:305–13.

    Google Scholar 

  183. Close DM, Patterson SS, Ripp S, Baek SJ, Sanseverino J, Sayler GS. Autonomous bioluminescent expression of the bacterial luciferase gene cassette (lux) in a mammalian cell line. PLoS One. 2010;5:e12441.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  184. Deluca M, Mcelroy WD. Two kinetically distinguishable ATP sites in firefly luciferase. Biochem Biophys Res Commun. 1984;123:764–70.

    Article  CAS  PubMed  Google Scholar 

  185. Seliger HH, Mcelroy WD. The colors of firefly bioluminescence: enzyme configuration and species specificity. Proc Natl Acad Sci U S A. 1964;52:75–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Bhaumik S, Lewis XZ, Gambhir SS. Optical imaging of Renilla luciferase, synthetic Renilla luciferase, and firefly luciferase reporter gene expression in living mice. J Biomed Opt. 2004;9:578–86.

    Article  CAS  PubMed  Google Scholar 

  187. Bowlby MR, Case JF. Ultrastructure and neuronal control of luminous cells in the copepod Gaussia princeps. Biol Bull. 1991;180:440–6.

    Article  CAS  PubMed  Google Scholar 

  188. Matthews JC, Hori K, Cormier MJ. Purification and properties of Renilla reniformis luciferase. Biochemistry. 1977;16:85–91.

    Article  CAS  PubMed  Google Scholar 

  189. Tannous BA, Kim DE, Fernandez JL, Weissleder R, Breakefield XO. Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo. Mol Ther. 2005;11:435–43.

    Article  CAS  PubMed  Google Scholar 

  190. Santos EB, Yeh R, Lee J, Nikhamin Y, Punzalan B, Punzalan B, La Perle K, Larson SM, Sadelain M, Brentjens RJ. Sensitive in vivo imaging of T cells using a membrane-bound Gaussia princeps luciferase. Nat Med. 2009;15:338–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Stacer AC, Nyati S, Moudgil P, Iyengar R, Luker KE, Rehemtulla A, Luker GD. NanoLuc reporter for dual luciferase imaging in living animals. Mol Imaging. 2013;12:1–13.

    Article  PubMed  CAS  Google Scholar 

  192. Luker GD, Bardill JP, Prior JL, Pica CM, Piwnica-Worms D, Leib DA. Noninvasive bioluminescence imaging of herpes simplex virus type 1 infection and therapy in living mice. J Virol. 2002;76:12149–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Saxena MT, Aton SJ, Hildebolt C, Prior JL, Abraham U, Piwnica-Worms D, Herzog ED. Bioluminescence imaging of period1 gene expression in utero. Mol Imaging. 2007;6:68–72.

    Article  CAS  PubMed  Google Scholar 

  194. Zhao H, Doyle TC, Wong RJ, Cao Y, Stevenson DK, Piwnica-Worms D, Contag CH. Characterization of coelenterazine analogs for measurements of Renilla luciferase activity in live cells and living animals. Mol Imaging. 2004;3:43–54.

    Article  CAS  PubMed  Google Scholar 

  195. Pichler A, Prior JL, Piwnica-Worms D. Imaging reversal of multidrug resistance in living mice with bioluminescence: MDR1 P-glycoprotein transports coelenterazine. Proc Natl Acad Sci U S A. 2004;101:1702–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Riedel CU, Monk IR, Casey PG, Morrissey D, O’sullivan GC, Tangney M, Hill C, Gahan CG. Improved luciferase tagging system for Listeria monocytogenes allows real-time monitoring in vivo and in vitro. Appl Environ Microbiol. 2007;73:3091–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Ur Rahman S, Stanton M, Casey PG, Spagnuolo A, Bensi G, Hill C, Francis KP, Tangney M, Gahan CG. Development of a click beetle luciferase reporter system for enhanced bioluminescence imaging of Listeria monocytogenes: analysis in cell culture and murine infection models. Front Microbiol. 2017;8:1797.

    Google Scholar 

  198. Fujii H, Noda K, Asami Y, Kuroda A, Sakata M, Tokida A. Increase in bioluminescence intensity of firefly luciferase using genetic modification. Anal Biochem. 2007;366:131–6.

    Article  CAS  PubMed  Google Scholar 

  199. Branchini BR, Ablamsky DM, Murtiashaw MH, Uzasci L, Fraga H, Southworth TL. Thermostable red and green light-producing firefly luciferase mutants for bioluminescent reporter applications. Anal Biochem. 2007;361:253–62.

    Article  CAS  PubMed  Google Scholar 

  200. Doyle TC, Nawotka KA, Purchio AF, Akin AR, Francis KP, Contag PR. Expression of firefly luciferase in Candida albicans and its use in the selection of stable transformants. Microb Pathog. 2006;40:69–81.

    Article  CAS  PubMed  Google Scholar 

  201. Enjalbert B, Rachini A, Vediyappan G, Pietrella D, Spaccapelo R, Vecchiarelli A, Brown AJ, D’enfert C. A multifunctional, synthetic Gaussia princeps luciferase reporter for live imaging of Candida albicans infections. Infect Immun. 2009;77:4847–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Branchini BR, Southworth TL, Khattak NF, Michelini E, Roda A. Red- and green-emitting firefly luciferase mutants for bioluminescent reporter applications. Anal Biochem. 2005;345:140–8.

    Article  CAS  PubMed  Google Scholar 

  203. Dorsaz S, Coste AT, Sanglard D. Red-shifted firefly luciferase optimized for Candida albicans in vivo bioluminescence imaging. Front Microbiol. 2017;8:1478.

    Google Scholar 

  204. Kadurugamuwa JL, Modi K, Coquoz O, Rice B, Smith S, Contag PR, Purchio T. Reduction of astrogliosis by early treatment of pneumococcal meningitis measured by simultaneous imaging, in vivo, of the pathogen and host response. Infect Immun. 2005;73:7836–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Shinde R, Perkins J, Contag CH. Luciferin derivatives for enhanced in vitro and in vivo bioluminescence assays. Biochemistry. 2006;45:11103–12.

    Article  CAS  PubMed  Google Scholar 

  206. Reddy GR, Thompson WC, Miller SC. Robust light emission from cyclic alkylaminoluciferin substrates for firefly luciferase. J Am Chem Soc. 2010;132:13586–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Takakura H, Sasakura K, Ueno T, Urano Y, Terai T, Hanaoka K, Tsuboi T, Nagano T. Development of luciferin analogues bearing an amino group and their application as BRET donors. Chem Asian J. 2010;5:2053–61.

    Article  CAS  PubMed  Google Scholar 

  208. Woodroofe CC, Shultz JW, Wood MG, Osterman J, Cali JJ, Daily WJ, Meisenheimer PL, Klaubert DH. N-Alkylated 6′-aminoluciferins are bioluminescent substrates for Ultra-Glo and QuantiLum luciferase: new potential scaffolds for bioluminescent assays. Biochemistry. 2008;47:10383–93.

    Article  CAS  PubMed  Google Scholar 

  209. Harwood KR, Mofford DM, Reddy GR, Miller SC. Identification of mutant firefly luciferases that efficiently utilize aminoluciferins. Chem Biol. 2011;18:1649–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Mofford DM, Reddy GR, Miller SC. Aminoluciferins extend firefly luciferase bioluminescence into the near-infrared and can be preferred substrates over D-luciferin. J Am Chem Soc. 2014;136:13277–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Adams ST Jr, Mofford DM, Reddy GS, Miller SC. Firefly luciferase mutants allow substrate-selective bioluminescence imaging in the mouse brain. Angew Chem Int Ed Engl. 2016;55:4943–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Nishihara R, Abe M, Nishiyama S, Citterio D, Suzuki K, Kim SB. Luciferase-specific coelenterazine analogues for optical contamination-free bioassays. Sci Rep. 2017;7:908.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  213. Otto-Duessel M, Khankaldyyan V, Gonzalez-Gomez I, Jensen MC, Laug WE, Rosol M. In vivo testing of Renilla luciferase substrate analogs in an orthotopic murine model of human glioblastoma. Mol Imaging. 2006;5:57–64.

    Article  PubMed  Google Scholar 

  214. Coleman SM, Mcgregor A. A bright future for bioluminescent imaging in viral research. Future Virol. 2015;10:169–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Luker KE, Schultz T, Romine J, Leib DA, Luker GD. Transgenic reporter mouse for bioluminescence imaging of herpes simplex virus 1 infection in living mice. Virology. 2006;347:286–95.

    Article  CAS  PubMed  Google Scholar 

  216. Mezzanotte L, van‘t Root M, Karatas H, Goun EA, Löwik CW. In vivo molecular bioluminescence imaging: new tools and applications. Trends Biotechnol. 2017;35:640–52.

    Article  CAS  PubMed  Google Scholar 

  217. Mezzanotte L, Que I, Kaijzel E, Branchini B, Roda A, Lowik C. Sensitive dual color in vivo bioluminescence imaging using a new red codon optimized firefly luciferase and a green click beetle luciferase. PLoS One. 2011;6:e19277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Inouye S, Shimomura O. The use of Renilla luciferase, Oplophorus luciferase, and apoaequorin as bioluminescent reporter protein in the presence of coelenterazine analogues as substrate. Biochem Biophys Res Commun. 1997;233:349–53.

    Article  CAS  PubMed  Google Scholar 

  219. Yeh HW, Karmach O, Ji A, Carter D, Martins-Green MM, Ai HW. Red-shifted luciferase-luciferin pairs for enhanced bioluminescence imaging. Nat Methods. 2017;14:971–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Conley NR, Dragulescu-Andrasi A, Rao J, Moerner WE. A selenium analogue of firefly D-luciferin with red-shifted bioluminescence emission. Angew Chem Int Ed Engl. 2012;51:3350–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Rumyantsev KA, Turoverov KK, Verkhusha VV. Near-infrared bioluminescent proteins for two-color multimodal imaging. Sci Rep. 2016;6:36588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Hickson J, Ackler S, Klaubert D, Bouska J, Ellis P, Foster K, Oleksijew A, Rodriguez L, Schlessinger S, Wang B, Frost D. Noninvasive molecular imaging of apoptosis in vivo using a modified firefly luciferase substrate, Z-DEVD-aminoluciferin. Cell Death Differ. 2010;17:1003–10.

    Article  CAS  PubMed  Google Scholar 

  223. Li J, Chen L, Du L, Li M. Cage the firefly luciferin! - a strategy for developing bioluminescent probes. Chem Soc Rev. 2013;42:662–76.

    Article  CAS  PubMed  Google Scholar 

  224. Dragulescu-Andrasi A, Liang G, Rao J. In vivo bioluminescence imaging of furin activity in breast cancer cells using bioluminogenic substrates. Bioconjug Chem. 2009;20:1660–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Shao Q, Jiang T, Ren G, Cheng Z, Xing B. Photoactivable bioluminescent probes for imaging luciferase activity. Chem Commun (Camb). 2009;(27):4028–30.

    Google Scholar 

  226. Chu J, Oh Y, Sens A, Ataie N, Dana H, Macklin JJ, Laviv T, Welf ES, Dean KM, Zhang F, Kim BB, Tang CT, Hu M, Baird MA, Davidson MW, Kay MA, Fiolka R, Yasuda R, Kim DS, Ng H-L, Lin MZ. A bright cyan-excitable orange fluorescent protein facilitates dual-emission microscopy and enhances bioluminescence imaging in vivo. Nat Biotechnol. 2016;34:760–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Dragulescu-Andrasi A, Chan CT, De A, Massoud TF, Gambhir SS. Bioluminescence resonance energy transfer (BRET) imaging of protein-protein interactions within deep tissues of living subjects. Proc Natl Acad Sci U S A. 2011;108:12060–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Farace C, Blanchot B, Champiat D, Couble P, Declercq G, Millet JL. Synthesis and characterization of a new substrate of Photinus pyralis luciferase: 4-methyl-D-luciferin. J Clin Chem Clin Biochem. 1990;28:471–4.

    CAS  PubMed  Google Scholar 

  229. Branchini BR, Murtiashaw MH, Magyar RA, Anderson SM. The role of lysine 529, a conserved residue of the acyl-adenylate-forming enzyme superfamily, in firefly luciferase. Biochemistry. 2000;39:5433–40.

    Article  CAS  PubMed  Google Scholar 

  230. Iwano S, Sugiyama M, Hama H, Watakabe A, Hasegawa N, Kuchimaru T, Tanaka KZ, Takahashi M, Ishida Y, Hata J, Shimozono S, Namiki K, Fukano T, Kiyama M, Okano H, Kizaka-Kondoh S, Mchugh TJ, Yamamori T, Hioki H, Maki S, Miyawaki A. Single-cell bioluminescence imaging of deep tissue in freely moving animals. Science. 2018;359:935–9.

    Article  CAS  PubMed  Google Scholar 

  231. Miura C, Kiyama M, Iwano S, Ito K, Obata R, Hirano T, Maki S, Niwa H. Synthesis and luminescence properties of biphenyl-type firefly luciferin analogs with a new, near-infrared light-emitting bioluminophore. Tetrahedron. 2013;69:9726–34.

    Article  CAS  Google Scholar 

  232. Skoura E, Zumla A, Bomanji J. Imaging in tuberculosis. Int J Infect Dis. 2015;32:87–93.

    Article  PubMed  Google Scholar 

  233. Lee KS, Im JG. CT in adults with tuberculosis of the chest: characteristic findings and role in management. AJR Am J Roentgenol. 1995;164:1361–7.

    Article  CAS  PubMed  Google Scholar 

  234. Hoffman EB, Crosier JH, Cremin BJ. Imaging in children with spinal tuberculosis. A comparison of radiography, computed tomography and magnetic resonance imaging. J Bone Joint Surg Br. 1993;75:233–9.

    Article  CAS  PubMed  Google Scholar 

  235. Soussan M, Brillet PY, Mekinian A, Khafagy A, Nicolas P, Vessieres A, Brauner M. Patterns of pulmonary tuberculosis on FDG-PET/CT. Eur J Radiol. 2012;81:2872–6.

    Article  PubMed  Google Scholar 

  236. Sule P, Tilvawala R, Behinaein P, Walkup GK, Cirillo JD. New directions using reporter enzyme fluorescence (REF) as a tuberculosis diagnostic platform. Tuberculosis (Edinb). 2016;101S:S78–82.

    Article  CAS  Google Scholar 

  237. Hugonnet JE, Tremblay LW, Boshoff HI, Barry CE 3rd, Blanchard JS. Meropenem-clavulanate is effective against extensively drug-resistant Mycobacterium tuberculosis. Science. 2009;323:1215–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  238. Davies J. Inactivation of antibiotics and the dissemination of resistance genes. Science. 1994;264:375–82.

    Article  CAS  PubMed  Google Scholar 

  239. Fisher JF, Mobashery S. Three decades of the class A beta-lactamase acyl-enzyme. Curr Protein Pept Sci. 2009;10:401–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. Hermann JC, Ridder L, Holtje HD, Mulholland AJ. Molecular mechanisms of antibiotic resistance: QM/MM modelling of deacylation in a class A beta-lactamase. Org Biomol Chem. 2006;4:206–10.

    Article  CAS  PubMed  Google Scholar 

  241. Knox JR, Moews PC, Frere JM. Molecular evolution of bacterial beta-lactam resistance. Chem Biol. 1996;3:937–47.

    Article  CAS  PubMed  Google Scholar 

  242. Boyd DB, Lunn WH. Electronic structures of cephalosporins and penicillins. 9. Departure of a leaving group in cephalosporins. J Med Chem. 1979;22:778–84.

    Article  CAS  PubMed  Google Scholar 

  243. Faraci WS, Pratt RF. Mechanism of inhibition of the PC1 beta-lactamase of Staphylococcus aureus by cephalosporins: importance of the 3′-leaving group. Biochemistry. 1985;24:903–10.

    Article  CAS  PubMed  Google Scholar 

  244. Wang F, Cassidy C, Sacchettini JC. Crystal structure and activity studies of the Mycobacterium tuberculosis beta-lactamase reveal its critical role in resistance to beta-lactam antibiotics. Antimicrob Agents Chemother. 2006;50:2762–71.

    Google Scholar 

  245. Xie H, Mire J, Kong Y, Chang M, Hassounah HA, Thornton CN, Sacchettini JC, Cirillo JD, Rao J. Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe. Nat Chem. 2012;4:802–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Cheng Y, Xie H, Sule P, Hassounah H, Graviss EA, Kong Y, Cirillo JD, Rao J. Fluorogenic probes with substitutions at the 2 and 7 positions of cephalosporin are highly BlaC-specific for rapid Mycobacterium tuberculosis detection. Angew Chem Int Ed Engl. 2014;53:9360–4.

    Article  CAS  PubMed  Google Scholar 

  247. Campbell RE. Realization of beta-lactamase as a versatile fluorogenic reporter. Trends Biotechnol. 2004;22:208–11.

    Article  CAS  PubMed  Google Scholar 

  248. Fry S, Barnabas S, Cotton MF. Update on trends in childhood tuberculosis. Curr Opin Pediatr. 2018;30:152–60.

    Article  PubMed  Google Scholar 

  249. Mufti N, Kong Y, Cirillo JD, Maitland KC. Fiber optic microendoscopy for preclinical study of bacterial infection dynamics. Biomed Opt Express. 2011;2:1121–34.

    Article  PubMed  PubMed Central  Google Scholar 

  250. Nooshabadi F, Yang HJ, Cheng Y, Durkee MS, Xie H, Rao J, Cirillo JD, Maitland KC. Intravital excitation increases detection sensitivity for pulmonary tuberculosis by whole-body imaging with beta-lactamase reporter enzyme fluorescence. J Biophotonics. 2017;10:821–9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Support for this work was from the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases, National Institutes of Health (grants HL115463 [to Y. K.] and AI104960 [to J. D. C.]; and the Bill and Melinda Gates Foundation (grant 48523 to J. D. C.).

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Authors and Affiliations

  1. Department of Microbial Pathogenesis and Immunology, Medical Research and Education Building, Texas A&M Health Science Center, Bryan, TX, USA

    Riti Sharan, Thushara Galbadage, Madeleine Moule & Preeti Sule

  2. Molecular and Human Genetics Department, Baylor College of Medicine, Houston, TX, USA

    Panatda Saenkham

  3. The University of Tennessee Health Science Center, Memphis, TN, USA

    Ying Kong

  4. Department of Microbial Pathogenesis and Immunology, Texas A&M University College of Medicine, Bryan, TX, USA

    Jeffrey D. Cirillo

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  1. Riti Sharan
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  2. Thushara Galbadage
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  4. Madeleine Moule
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  5. Preeti Sule
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  6. Ying Kong
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  7. Jeffrey D. Cirillo
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Correspondence to Ying Kong or Jeffrey D. Cirillo .

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  1. Department of Microbial Pathogenesis and Immunology, Texas A&M University College of Medicine, Bryan, TX, USA

    Jeffrey D. Cirillo

  2. The University of Tennessee Health Science Center, Memphis, TN, USA

    Ying Kong

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Sharan, R. et al. (2019). Optical In Vivo Imaging in Tuberculosis Research. In: Cirillo, J., Kong, Y. (eds) Tuberculosis Host-Pathogen Interactions. Springer, Cham. https://doi.org/10.1007/978-3-030-25381-3_8

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