Monday, September 24, 2018

BacterioFiles 356 - Beams Boost Bolstered Bacteria

tumor-targeting bacterium
From: Zheng et al. 2018,
Nat Commun 9:1680
This episode: Combining cells with light-absorbing nanomaterials can help tumor-targeting bacteria produce more anticancer compound!

Download Episode (10.4 MB, 11.4 minutes)

Show notes:
Microbe of the episode: Maruca vitrata nucleopolyhedrovirus

Here's a paper I found that actually shows carbon dot nanomaterials enhancing bacterial nitrogen fixation

Journal Paper:
Zheng D-W, Chen Y, Li Z-H, Xu L, Li C-X, Li B, Fan J-X, Cheng S-X, Zhang X-Z. 2018. Optically-controlled bacterial metabolite for cancer therapy. Nat Commun 9:1680.

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Episode outline:
  • Background: Using bacteria to treat cancer is very promising
    • Some options just go all over and attack tumors selectively
    • Some can be guided, like magnetotaxis
    • Attach nanomaterials to target tumors, or engineer to produce anticancer compounds
  • But can be hard to deliver adequate amounts
    • Can't carry very much, and hard to get stable in situ production
    • Hard to get enough electrons/energy to microbes in tumor environment
  • What’s new: Now, scientists publishing in Nature Communications have created cyborg cancer-seeking bacteria that can absorb light energy to generate tumor-killing compounds!
  • Methods: Took nonpathogenic strain of Escherichia coli, MG1655
    • Already good at tumor targeting
    • And has enzyme called nitrate reductase
      • Adds electrons to nitrate ions, NO3-, can produce nitric oxide, NO
      • Reactive compound, immune system produces to kill targets
      • Making a lot locally can kill cancer
      • But requires lots of electrons
  • Bound bacteria to carbon-dot doped carbon nitride
    • Nanomaterial semiconductor substance made of carbons and nitrogens in a matrix
    • Carbon dots – carbon-based nanoparticles, absorb/interact with light
    • So can absorb light and pass energy to bacteria by generating electron flow to enzymes
  • Tested this combo with chemical test – reagent turns red if NO generated
    • In light, combo generated a lot; bacteria or nanomaterial alone not as much
      • Made enough NO in 15 min to kill cancer cells
    • In dark, a lot less from combo
  • Could measure current generated by nanomaterial, and rise in electron stores of bacteria
    • And confirmed generation of NO from nitrate with 15-N nitrate
    • Found similar effect could be achieved with CdS nanoparticles + bacteria
  • Tested system in vitro – 3D-printed setup 
    • cancer cells in chamber surrounded by bacterial culture
    • NO could diffuse through membrane between
    • Could detect it in the cells with fluorescent detector compound
    • Also observed cancer viability decreasing, up to 70% of cells killed in 24h
    • Bacteria without the nanomaterial, or in dark, didn't kill
  • Then tried in vivo – in mice with tumors
    • Injected bacteria, detected fluorescence from them localized to tumor
    • Negligible in liver and elsewhere
  • But does it penetrate tumor tissue? Many synthetic carriers don't
    • Sectioned samples to see how far in
    • Actually most bacteria penetrated all the way in
  • Bacteria cleared from mice within 3 weeks, and no side effects detected
    • Antibiotics could help clear too
  • And NO was produced – set up tumors to produce bioluminescence in response
  • So how well does it work?
    • Saw correlation between bacteria, NO, and tumor cell death
    • Inhibited 70-80% of tumor growth in mice
    • Nanomaterial and bacteria alone not very effective
    • But together, produced NO that killed cells even at a distance
    • Seemed to induce stronger immune response against cancer too
  • Summary: Combined tumor-seeking bacteria with nanomaterial that absorbs light and uses it to generate electron flow, allowing bacteria to produce NO in tumor that kills it
  • Applications and implications: Potentially useful system for cancer treatment
    • If safe and effective in humans
  • Electron flux is important for other things too
    • Like nitrogen fixation; maybe help fertilize crops
  • What do I think: Fascinating way to combine best of nanotechnology with microbiology
  • Hope to see more in future

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