Skip to main content

Advertisement

Log in

Bacterial bioluminescence assay for bioanalysis and bioimaging

  • Trends
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Bioluminescence occurs through a chemical reaction in organisms that spontaneously produce light. Luminescent bacteria are unique among bioluminescent organisms. Their bioluminescence intensity is an indicator of their metabolic activity, which can directly reflect the influence of environmental factors on cell viability. Moreover, the whole bioluminescence process is totally gene encoded without the addition of extra substrates. As a result, bacterial bioluminescence has been a powerful tool for whole-cell biosensors and bio-reporters in bioanalysis and bioimaging. This review aims to cover the applications of wild-type and recombinant luminescent bacteria to detect the toxicity of environmental pollutants and biological molecules. The bacterial bioluminescence analytical assay has characteristics such as high sensitivity, short-term detection, and easy operation. Meanwhile, due to the development of gene engineering and optical technology, bacterial luciferase as a reporter protein has been successfully expressed in prokaryotic and eukaryotic cells, tissues, and organs of animals. The major applications for bacterial luciferase-based bioluminescence imaging, such as infectious diseases, cancer therapy, and stem cell tracing, are discussed in this review.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Haddock SHD, Moline MA, Case JF. Bioluminescence in the Sea. Annu Rev Mar Sci. 2010;2:443–93.

    Article  Google Scholar 

  2. Namkung Y, Gouill CL, Lukashova V, Kobayashi H, Hogue M, Khoury E, et al. Monitoring G protein-coupled receptor and β-arrestin trafficking in live cells using enhanced bystander BRET. Nat Commun. 2016;7:12178.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wang F, Li Z, Yang YY, Wan D, Hammock BD. Chemiluminescent enzyme immunoassay and bioluminescent enzyme immunoassay for tenuazonic acid mycotoxin by exploitation of nanobody and nanobody-nanoluciferase fusion. Anal Chem. 2020;92(17):11935–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Iwano S, Sugiyama M, Hama H, Watakabe A, Hasegawa N, Kuchimaru T, et al. Single-cell bioluminescence imaging of deep tissue in freely moving animals. Science. 2018;359(6378):935.

    Article  CAS  PubMed  Google Scholar 

  5. Shimomura O. Bioluminescence: chemical principles and methods. Singapore: World Scientific Publishing Co. Pte. Ltd; 2006.

    Book  Google Scholar 

  6. Cong H, Liu Y, Ferré N, Fang W. Understanding bacterial bioluminescence: a theoretical study of the entire process, from reduced flavin to light emission. Chem-Eur J. 2014;20(26):7979–86.

    Article  Google Scholar 

  7. Lee J. Perspectives on bioluminescence mechanisms. Photochem Photobiol. 2017;93(2):389–404.

    Article  CAS  PubMed  Google Scholar 

  8. Su Y, Walker JR, Park Y, Smith TP, Lin MZ. Novel NanoLuc substrates enable bright two-population bioluminescence imaging in animals. Nat Methods. 2020;17(8):852–60.

    Article  CAS  PubMed  Google Scholar 

  9. Li JB, Liu HW, Fu T, Wang R, Tan W. Recent progress in small-molecule near-IR probes for bioimaging. Trend Chem. 2019;1(2):224–34.

    Article  CAS  Google Scholar 

  10. Li J, Chen L, Du L, Li M. Cage the firefly luciferin! – a strategy for developing bioluminescent probes. Chem Soc Rev. 2012;42(2):662–76.

    Article  Google Scholar 

  11. Yampolsky IV, Kaskova ZM, et al. 1001 lights: luciferins, luciferases, their mechanisms of action and applications in chemical analysis, biology and medicine. Chem Soc Rev. 2016;45:6048.

    Article  PubMed  Google Scholar 

  12. Roda A, Guardigli M, Michelini E, Mirasoli M. Bioluminescence in analytical chemistry and in vivo imaging. Trac-Trends Anal Chem. 2009;28(3):307–22.

    Article  CAS  Google Scholar 

  13. Abbas M, Adil M, Ehtisham-ul-Haque S, Munir B, Yameen M, Ghaffar A, et al. Vibrio fischeri bioluminescence inhibition assay for ecotoxicity assessment: a review. Sci Total Environ. 2018;626:1295–309.

    Article  CAS  PubMed  Google Scholar 

  14. Close D, Xu TT, Smartt A, Rogers A, Crossley R, Price S, et al. The evolution of the bacterial luciferase gene cassette (lux) as a real-time bioreporter. Sensors (Basel). 2012;12(1):732–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vlastos D, Antonopoulou M, Konstantinou I. Evaluation of toxicity and genotoxicity of 2-chlorophenol on bacteria, fish and human cells. Sci Total Environ. 2016;551:649–55.

    Article  PubMed  Google Scholar 

  16. Muneeswaran T, Kalyanaraman N, Vennila T, Kannan MR, Ramakritinan CM. Rapid assessment of heavy metal toxicity using bioluminescent bacteria Photobacterium leiognathi strain GoMGm1. Environ Monit Assess. 2021;193(3):109.

    Article  CAS  PubMed  Google Scholar 

  17. Cui ZS, Luan X, Jiang HC, Li Q, Xu GF, Sun CJ, et al. Application of a bacterial whole cell biosensor for the rapid detection of cytotoxicity in heavy metal contaminated seawater. Chemosphere. 2018;200:322–9.

    Article  CAS  PubMed  Google Scholar 

  18. Singh A, Kumar V. Recent advances in synthetic biology-enabled and natural whole-cell optical biosensing of heavy metals. Anal Bioanal Chem. 2020;413:73–82.

    Article  PubMed  Google Scholar 

  19. Qiu TA, Nguyen T, Hudson-Smith NV, Clement PL, Forester DC, Frew H, et al. Growth-based bacterial viability assay for interference-free and high-throughput toxicity screening of nanomaterials. Anal Chem. 2017;89(3):2057–64.

    Article  CAS  PubMed  Google Scholar 

  20. Zhang H, Shi J, Su Y, Li W, Xie B. Acute toxicity evaluation of nanoparticles mixtures using luminescent bacteria. Environ Monit Assess. 2020;192(8):484.

    Article  CAS  PubMed  Google Scholar 

  21. Hayek M, Baraquet C, Lami R, Blache Y, Molmeret M. The marine bacterium Shewanella woodyi produces C8-HSL to regulate bioluminescence. Micro Ecol. 2020;79:865–81.

    Article  CAS  Google Scholar 

  22. Eickhoff MJ, Bassler BL. SnapShot: Bacterial Quorum Sensing. Cell. 2018;174(5):1328–1328.e1.

    Article  CAS  PubMed  Google Scholar 

  23. Annotation and quantification of N -acyl homoserine lactones implied in bacterial quorum sensing by supercritical-fluid chromatography coupled with high-resolution mass spectrometry. Anal Bioanal Chem. 2020;412(10):2261–76.

  24. Kumari A, Pasini P, Daunert S. Detection of bacterial quorum sensing N-acyl homoserine lactones in clinical samples. Anal Bioanal Chem. 2008;391(5):1619–27.

    Article  CAS  PubMed  Google Scholar 

  25. Mm A, Vf B, Zb A, In A, Fk A, Rm A, et al. Cyclodextrin-mediated quorum quenching in the Aliivibrio fischeri bioluminescence model system – modulation of bacterial communication. Int J Pharm. 2021;594:120150.

    Article  Google Scholar 

  26. Makabenta J, Nabawy A, Li CH, Schmidt-Malan S, Rotello VM. Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections. Nat Rev Microbiol. 2020;19:23–36.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Theuretzbacher U, Ou Tt Erson K, Engel A, Karlén A. The global preclinical antibacterial pipeline. Nat Rev Microbiol. 2019;18(6):275–85.

    PubMed  PubMed Central  Google Scholar 

  28. Li M, Wei D, Du Y. Acute toxicity evaluation for quinolone antibiotics and their chlorination disinfection processes. J Environ Sci. 2014;26(9):1837–42.

    Article  Google Scholar 

  29. Tong F, Zhao Y, Gu X, Gu C, Lee CCC. Joint toxicity of tetracycline with copper(II) and cadmium(II) to Vibrio fischeri: effect of complexation reaction. Ecotoxicology. 2015;24(2):346–55.

    Article  CAS  PubMed  Google Scholar 

  30. Kotlobay AA, Sarkisyan KS, Mokrushina YA, Marcet-Houben M, Serebrovskaya EO, Markina NM, et al. Genetically encodable bioluminescent system from fungi. Proc Natl Acad Sci U S A. 2018;115(50):12728–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yagur-Kroll S, Belkin S. Upgrading bioluminescent bacterial bioreporter performance by splitting the lux operon. Anal Bioanal Chem. 2011;400(4):1071–82.

    Article  CAS  PubMed  Google Scholar 

  32. Gregor C, Gwosch KC, Sahl SJ, Hell SW. Strongly enhanced bacterial bioluminescence with the ilux operon for single-cell imaging. Proc Natl Acad Sci U S A. 2018;115(5):962–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gregor C, Pape JK, Gwosch KC, Gilat T, Sahl SJ, Hell SW. Autonomous bioluminescence imaging of single mammalian cells with the bacterial bioluminescence system. Proc Natl Acad Sci U S A. 2019;116(52):26491–6.

    Article  CAS  PubMed Central  Google Scholar 

  34. Belas R, Mileham A, Cohn D, Hilmen M, Simon M, Silverman M. Bacterial bioluminescence-isolation and expression of the luciferase genes from vibrio-harveyi. Science. 1982;218(4574):791–3.

    Article  CAS  PubMed  Google Scholar 

  35. Wang X, Li Z, Li B, Chi H, Li J, Fan 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(4):519–26.

    Article  CAS  PubMed  Google Scholar 

  36. Kaku T, Sugiura K, Entani T, Osabe K, Nagai T. Enhanced brightness of bacterial luciferase by bioluminescence resonance energy transfer. Sci Rep. 2021;11(1):14994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mitiouchkina T, Mishin AS, Somermeyer LG, Markina NM, Chepurnyh TV, Guglya EB, et al. Plants with genetically encoded autoluminescence. Nat Biotechnol. 2020;38:944–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tian X, Gao Y, Wang S, Hameed H, Zhang T. Rapid visualized assessment of drug efficacy in live mice with a selectable marker-free autoluminescent Klebsiella pneumoniae. Biosens Bioelectron. 2021;177:112919.

    Article  CAS  PubMed  Google Scholar 

  39. Min JJ, Nguyen VH, Kim HJ, Hong Y, Choy HE. Quantitative bioluminescence imaging of tumor-targeting bacteria in living animals. Nat Protoc. 2008;3:629–36.

    Article  CAS  PubMed  Google Scholar 

  40. Contag CH, Contag PR, Mullins JI, Spilman SD, Stevenson DK, Benaron DA. Photonic detection of bacterial pathogens in living hosts. Mol Microbiol. 1995;18(4):593–603.

    Article  CAS  PubMed  Google Scholar 

  41. Seok HN, Man HO, et al. Imaging of bioluminescent Acinetobacter baumannii in a mouse pneumonia model. Microb Pathogenesis. 2019;137:103784.

    Article  Google Scholar 

  42. Kadurugamuwa JL, Modi K, Coquoz O, Rice B, Smith S, Contag PR, et al. 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(12):7836–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Agrawal N, Bettegowda C, Cheong I, Geschwind JF, Vogelstein B. Bacteriolytic therapy can generate a potent immune response against experimental tumors. Proc Natl Acad Sci U S A. 2004;101(42):15172–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Yazawa K, Fujimori M, Amano J, Kano Y, Taniguchi S. Bifidobacterium longum as a delivery system for cancer gene therapy: selective localization and growth in hypoxic tumors. Cancer Gene Ther. 2000;7(2):269–74.

    Article  CAS  PubMed  Google Scholar 

  45. Kaemmer CA, Umesalma S, Maharjan CK, Moose DL, Quelle DE. Development and comparison of novel bioluminescent mouse models of pancreatic neuroendocrine neoplasm metastasis. Sci Rep. 2021;11:10252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Rex JH, Lynch HF, Cohen IG, Darrow JJ, Outterson K. Designing development programs for non-traditional antibacterial agents. Nat Commun. 2019;10:3416.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Ren Y, Qiang Y, Zhu B, Tang W, Duan X, Li Z. General strategy for bioluminescence sensing of peptidase activity In vivo based on tumor-targeting probiotic. Anal Chem. 2021;93(9):4334–41.

    Article  CAS  PubMed  Google Scholar 

  48. Cronin M, Akin AR, Collins SA, Meganck J, Kim JB, Baban CK, et al. High resolution in vivo bioluminescent imaging for the study of bacterial tumour targeting. PLoS One. 2012;7(1):e30940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Conway M, Xu T, Kirkpatrick A, Ripp S, Close D. Real-time tracking of stem cell viability, proliferation, and differentiation with autonomous bioluminescence imaging. BMC Biol. 2020;18(1):79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work received financial supports from the National Natural Science Foundation of China (Grants 21874070 and 21925403).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wei Wang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Published in the topical collection celebrating ABCs 20th Anniversary.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., He, X., Zhu, W. et al. Bacterial bioluminescence assay for bioanalysis and bioimaging. Anal Bioanal Chem 414, 75–83 (2022). https://doi.org/10.1007/s00216-021-03695-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-021-03695-9

Keywords

Navigation