BLI and cancer #1


Recently, more than one bacteria strain has been described to germinate and grow only in the hypoxic regions of solid tumours.

It comes to mind the ancient 1890s when Dr WB Coley observed tumour regression after postoperative bacterial infections. The tricky question now is: does bacteria should be a new weapon against cancer? It is conceivable a cancer therapy employing safe-bacteria as magic bullets? To get off the ground, we need first a tool to visualize the process of bacterial-tumour targeting, to quantify bacterial growth in target tissues (better if non invasively), and to monitor bacterial migration in real-time. Bioluminescence imaging? Yes, of course: which other tech is becoming such cornerstone in biomedical investigation?

Nowadays, JJ Min and colleagues from Chonnam National University introduce in Nature Protocols a detailed “how to” for imaging bacterial luciferase (lux) expressing bacteria in small living animals. This genetic engineering and imaging protocol would be a powerful approach for the quantitative visualization of the distribution of bacteria in mouse tumour models.

What about the reporter gene? Compared to more celebrated luciferases, the advantage of the lux luciferase is that it does not require any exogenous source of substrate to produce bioluminescence, and this would be a plus in some hidden niches of tissues where the substrate should be difficult to administer. But some possible drawbacks need to be considered:
  1. the weight: in fact it is more correct to refer to lux luciferase as to the “lux operon”, because such complex is more than one enzyme: the lux operon (like the lux CDABE from Photobacterium leiognathi) encodes, in roughly 10 kb, several proteins required for the bioluminescence, including bacterial luciferase, the substrate producer and the substrate-regenerating enzymes. Managing 10 kb in your vector needs some mastering abilities (and some space).
  2. the light: the light color is bluish-white, a hue strongly absorbed by mammalian tissues because of the haemoglobin. This would really hamper the sensitivity of the system in vivo.
  3. the oxygen paucity: yes, bacterial luciferases require oxygen, an asset in the hypoxic regions of tumours!

Min, J., Nguyen, V.H., Kim, H., Hong, Y., Choy, H.E. (2008). Quantitative bioluminescence imaging of tumor-targeting bacteria in living animals. Nature Protocols, 3(4), 629-636. DOI: 10.1038/nprot.2008.32