Monday, February 12, 2018

BacterioFiles 328 - Focused Phages Fight Films

By Sherwood Casjens,Elaine Lenk
CC BY-SA 3.0
This episode: Phages bound to magnetic nanoparticles can be guided and pulled toward their target, penetrating biofilms to kill harmful microbes!

Download Episode (9.6 MB, 10.4 minutes)

Show notes:
Microbe of the episode: Veillonella alcalescens

News item

Journal Paper:
Li L-L, Yu P, Wang X, Yu S-S, Mathieu J, Yu H-Q, Alvarez PJJ. 2017. Enhanced biofilm penetration for microbial control by polyvalent phages conjugated with magnetic colloidal nanoparticle clusters (CNCs). Environ Sci Nano 4:1817–1826.

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  • Post questions or comments here or email to Thanks for listening!

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    Episode outline:

    • Background: Microbes very good at surviving tough environments
      • Fascinating abilities, but not always positive: pathogens
    • One trick is making biofilms to live in
      • Protect selves from predators and toxins (like white blood cells or antibiotics)
      • Pretty tough to disrupt established pathogen biofilms in body, hard to treat
    • What’s new: Now, scientists publishing in Environmental Science: Nano have developed a new approach to biofilm treatment: using bacteriophages with magnetic nanoparticle clusters!
    • Plenty of research into using phages as treatment
      • Specific (but some have more broad host range), self-propagating, go away on their own
    • Problems with it
      • Getting phages to the right place in the body in good amounts
      • Phages also have trouble getting through biofilms
    • Methods: So here, attached magnetic colloidal nanoparticle clusters or CNCs to phages
      • Can use magnets to guide phage-cluster combos into biofilm to their targets
    • Phage PEL1, infects both E. coli and Pseudomonas aeruginosa used to test
      • Attached to iron oxide clusters treated various ways
        • Chose chitosan-coated clusters cos better infectivity properties
      • Made sure it didn’t affect phage function/infection with plaque assays
      • Also made sure particles attached to phage head instead of tail
    • Then tested effectiveness against biofilms
      • Unmodified phages reduced area ~35%
      • Clusters alone 10%
      • Mixed together, about 71%
      • But attached together, almost 90%
      • Clusters help phages penetrate and stick around long enough to infect
    • Then tested again applying magnetic field to direct phages
      • Clusters like tiny magnets
      • Field ~7 strong fridge magnets in strength
      • Could affect shape of plaques formed by field direction
    • Summary: Phages bound to magnetic particles more effective at penetrating to and killing pathogens in biofilms
    • Applications and implications: Medical, industrial (fouling)
      • Phage therapy more targeted/versatile, but easier to resist sometimes
      • No harmful residue
      • This makes better for dealing with biofilms
    • Industrially, put in a few phages and then guide around with magnets
    • Improvements: modified phages, multiple types, combo with antibiotics, degrading enzymes
    • Clarifications if necessary: Not tested out in target places yet
    • What do I think: Good plan to enhance phages, overcome some limitations (targeting)
    • More effective killing machines


    1. Hello Dr. Noar,
      I enjoyed listening to this weeks episode. So, just to recap to make sure that I am understanding correctly. When phages are modified with the clusters and coated with the magnetic nanoparticles it is possible to direct the phages to target certain areas? How could this hypothetically work in the human body? Would the phages be introduced through a capsule so that it wouldn't dissolve in the stomach acids and would pass on to the intestine? Or would it be delivered through an injection? Also, would it be possible to direct the modified phages by the use of imaging technology such as a concentrated MRI scan?

      Thank you,
      Zoe Wafford

      1. Hi Zoe,

        You have understood correctly, and also brought up some good questions and challenges that would need to be answered to make this into an effective treatment!

        Pill and injection could both possibly work as routes of administering the phage, and it might depend on what is being treated and where in the body. Or a pill might be sufficient for everything--to preview an upcoming episode, it's possible that bacteriophages might be able to move fairly freely through the body!

        How to direct them once inside is another important challenge, one that's a bit outside of my field of knowledge. I would think that applying a magnetic field that's directed enough toward the target site, the phages could get there eventually, but whether that could happen in a reasonable amount of time, I'm not sure. Perhaps a situation like with Iron Man wearing a magnet to pull particles to one particular place, except unfortunately this probably wouldn't make you a superhero, haha. There are researchers working on similar versions of this question though:

        Thanks for listening!

    2. How likely do you think it will be that we will see phages being used to cure bigger disease, such as cancer, in the future?

      1. Well, bacteriophages infect microbes very specifically, so if the goal were to kill cancer and such by infecting it, phages probably wouldn't be a very good choice. However, other viruses are much more promising as treatments for cancer, especially ones that can specifically exploit the cancer's deficiencies while not having much effect on healthy cells. One of these that has been investigated is actually measles!

        Another oncolytic virus, as they're called, has actually been approved by the FDA for treatment of melanoma skin cancer:

        So that's pretty exciting stuff.

        If the goal isn't infecting so much as, perhaps, delivering anticancer therapies directly to cancer cells in the body, phages might have more effect as a kind of nanomachine, but I don't really know if they would have any advantages over other types of nanoparticle for this purpose.

        Lastly, cancer may be a bigger thing now, but if we're not more careful about antibiotic use, infection with drug-resistant bacteria could become a very big deal itself, like bacterial infection used to be in the time before antibiotics! So developing phages as another, more targeted and versatile way to treat infections is a very important thing to study now in itself.

    3. What type of targeting mechanisms do you think will be most impacted by these findings?

      1. Not sure what you mean by targeting mechanisms, but overall I think this approach could have the most effect in treating very localized infections in the body, especially those involving biofilms like in the lungs of patients with cystic fibrosis. It could also be useful in industrial settings to prevent bacteria from building up gunk in pipes and such and causing problems or contamination.