P. aeruginosa, Biofilms and Honey

ResearchBlogging.org

In what will be the first of a few articles inspired from my recent soirée in old Sydney town I want to talk today about biofilms. Biofilms were a focal point for the conference and I got to hear a lot about who makes them, why they are made, the maturation of biofilms, what happens when opposing species biofilms interact, biofilms underwater, biofilms on organic material and on man-made surfaces, how we can kill organisms within them, how we can break-up a biofilm and honey. But maybe it’s worth starting at the beginning. What’s a biofilm?

A biofilm is generally described as a ‘synthesised environment housing a bacterial community on a surface’. This essentially means that organisms (not just bacteria) start to produce huge amount of ‘muck’ containing proteins, sugars and DNA and export it from the cell once bound to a ‘surface’. When it does this it generates its own little environmental niche and as that bacterial cell divides within the biofilm it can pool its resources allowing easier growth for the community as a whole. It also has other effects. Biofilms are largely resistant to disinfection and antibiotics as the bacteria can keep the actual environment at bay whilst happily existing in its own filth.

Before I continue the story here, and get to the disease part, I want to talk about biofilm maturation as it allows me to show one of the coolest pics I remember from my undergraduate days.

Biofilm maturation is really important and in some ways very similar to fungal spore spread and even shares some similarities to natural plant seed distribution. Immature biofilms begin at the surface and grow as a patch of cells. As the cell number increases the bacteria begin to signal each other the mature the biofilm and the cells start to pile up on each other. Eventually the bacteria form a large ‘stalking’ structure with a ‘head’. The biofilm at the head is slightly thinner and is the source of ‘seeding cells’ which can be removed by the passing environment (wind, water etc.) to land on a new or distant surfaces to start a new colony and biofilm. In hindsight that pic isn’t that cool at all. Forget I said anything.

ANYWAY…

What’s the big deal with biofilms anyway? Aside from being environmentally important, the source of potential anti-microbials and interesting from an evolutionary perspective they are also hugely medically relevant.

I want to talk about to talk about the biofilm produced by a bacteria called Pseudomonas aeruginosa under a couple of different conditions to show why its so important.

Let’s start with implants. Not those implants, get your mind out the gutter.

P. aeruginosa is the one of the leading causes of biofilms caused by implanted medical equipment, such as catheters, pacemakers and okay, fine, yes, those implants too.

This is a really interesting situation as the surface is man-made and the bacterium has not co-evolved alongside medical grade plastics for very long. Despite this, the biofilms develop very quickly on these surfaces, often resulting in patients being placed on huge quantities of anti-biotics and in some cases the implants must be removed again due to the bacterial load and the health implications to already very sick patients.

The second condition I want to mention is with burns patients. Ever wondered why you not allowed to bring flowers to burns patients?

P. aeruginosa normally lives in the ground, in fact its super common in the ground. It loves the Earth, but think about a wound, particularly a burn. Moist, warm and nutrient rich, bacteria and wounds are like Jay-Z and New York, they like where they live . P. aeruginosa is particularly adept at living in burns and when it does so produces his thick green-black biofilm which becomes a real issue for the burns patient. Remember, these people are already sick, an bacterial community impervious to antimicrobials is the last thing they need.

Finally, and this was a particularly overly represented topic in Sydney, is P. aeruginosa and Cystic Fibrosis. We haven’t had an opportunity to discuss CF yet but one aspect of this devastating genetic condition is that the ciliated cells in the lung don’t function normally. The result is that the mucous you produce isn’t removed from the lung effectively. This provides a nutrient rich environment for P. aeruginosa and other species to live in and the biofilms produced during these infections make it impossible to remove the resident P. aeruginosa once established. By early teenage-hood CF patients have established an infection with P. aeruginosa they will carry for the rest of their lives. As I have mentioned a number of times now the anti-microbial nature of the biofilm ensures the persistence of this infection whilst also adding significant quantities of extra product to a lung which can’t even move its own mucous out of the way.

Rather than end on that slightly down note I’d prefer end on something positive. You know what that, as well as having broad range anti-microbial activity, can break up and disperse biofilms? Honey. Specifically, Manuka Honey.

Suck it bees, we're stealing your honey to rub on our sores <http://www.flickr.com/photos/austinevan/3168742874/&gt;

I had heard about this before but assumed that it was one of those old wives tales. Honey has coped a bad rap in the past, particularly with all that nonsense about ‘Royal Jelly’ but there is actual, real, scientific proof of the power of honey. I won’t go into the specifics of it here (but you can find out more here) but honey is made up of a large number of chemicals and many of them are bio-active and anti-microbial. Its also at an inhospitable pH for bacterial growth and has a low water activity rating, a fancy way of saying that its more likely to suck water out of stuff than stuff is likely to suck water out of it. Oh and if you a medical student you might want to check out this picture below, and the link provided with it. Make sure you suggest honey treatment for your next major wound to score innovative thinking points with your supervisor.

Before and after shot of topical honey treatment for 3 weeks. You're welcome. Adapted from Efem (1988)

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Efem, S. (1988). Clinical observations on the wound healing properties of honey British Journal of Surgery, 75 (7), 679-681 DOI: 10.1002/bjs.1800750718
Bielecki, P., Glik, J., Kawecki, M., & Martins dos Santos, V. (2007). Towards understanding Pseudomonas aeruginosa burn wound infections by profiling gene expression Biotechnology Letters, 30 (5), 777-790 DOI: 10.1007/s10529-007-9620-2
PITTET, B., MONTANDON, D., & PITTET, D. (2005). Infection in breast implants The Lancet Infectious Diseases, 5 (2), 94-106 DOI: 10.1016/S1473-3099(05)01281-8

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26 Comments

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26 responses to “P. aeruginosa, Biofilms and Honey

  1. Pingback: Tweets that mention P. aeruginosa, Biofilms and Honey « Disease of the Week! -- Topsy.com

  2. Biofilms make for fascinating research, semi-multicellular activity from bacteria. I’d heard about honey being an effective antibacterial, but I didn’t know it was also effective against biofilms. Great write-up.

    • OMG THE Lab Rat! I am such a big fan of your blog!
      cough cough
      I don’t know how convinced I am of the dispersive properties of honey but I think any activity it might have over other therapeutics is due to the multi-pronged nature of honey’s own activity. Of particular importance to upsetting a biofilm would be water and solute activity within the biofilm. As honey has such a low water activity my guess would be thats where honey gets a foothold and dispersion follows as the bacterial community begins to wither. Having said that my professional opinion is “/shoulder shrug”
      Its nice to know our blog is being read at all but its nice to see it being read by other bloggers, after a rubbish day at the bench this has brightened my day considerably :)

  3. One of the most effective agents against biofilms is NO and nitrite. NO specifically triggers the transition from the biofilm phenotype to the planktonic phenotype.

    http://jb.asm.org/cgi/content/full/188/21/7344?view=long&pmid=17050922

    Nitrite added to biofilms causes them to disperse, even without killing the bacteria. I discuss this phenomena and have links to the literature on it in my blog on using a biofilm of bacteria that generate NO and nitrite (autotrophic ammonia oxidizing bacteria) to suppress skin infections.

    http://daedalus2u.blogspot.com/2008/06/suggestion-to-reduce-antibiotic.html

    Many fluids in plants have significant nitrate. This would be concentrated along with the sugars as water is removed. Nitrate in honey being reduced to nitrite and NO might be an important pathway in the biofilm dispersal properties of honey.

    • Your absolutely right but I wonder how reactive honey is compared to other sources of NO burst? I haven’t seen any data on this, do you know of any?
      I am aware that honey has potent H2O2 capabilities however which may compensate for NO if it is lacking.

      • Saliva after a high nitrate meal can have 2 mM/L nitrite. On skin, nitrite is reduced to NO pretty quickly, the low pH and the presence of xanthine oxidoreductase.

        That is thought to be the reason behind why animals and people lick wounds.

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  10. K

    I am a mother of a child who has Cystic Fibrosis. I have been giving my daughter Manuka Honey since she was just over a year old for its many health benefits.

    Recently, I have come across a few articles that talk about Manuka Honey and Cystic Fibrosis and I am wondering if you can help me to sort out the contents (since I have a very limited science background).

    Do you know of any specific studies that are looking at Manuka Honey and Cystic Fibrosis? To be effective against bacteria such as Pseudemonas, would it have to be inhaled?

    • Hi K,
      I had a bit of a look around and couldn’t find anything specifically about the use of honey to treat CF infections. That being said there were a few papers that removed mucosal samples from patients and tested susceptibility to honey diluted to as little as 6% and found that honey could inhibit bacterial growth in most cases and cause bacterial cell death in others. The problem these studies indicated is that the honey has to have one of its most potent weapons, hydrogen peroxide, removed. If the hydrogen peroxide is left in the honey then it can actually make things worse by prompting species such as Pseudomonas to defend themselves. One particularly bad defence mechanism is for the bacteria to convert to a mucoid phenotype that essentially creates a better biofilm and will have the effect of making the infection much worse.
      As neither Thomas or I are medical professionals we can only give our interpretation of the scientific data as we see it but that does not mean we have read everything and I would strongly encourage you raising the prospect of honey treatments with your daughters specialist if you think it might be a possible option.

    • Cheri

      Hi, Have you found any more information about manuka honey and cf? My 17yo son has been eating it for a while and I have thought about dissolving it in his nebulizer lol. If it can be used for sinus rinses, I wonder if it can be used to inhale. I did read the response to your question. Send me an email… I’d love to chat about it. swan9499@yahoo.com Thanks!

      • Hi Cheri,
        I haven’t found any more info on the topic of CF and Manuka honey beyond what I have written here. I don’t think I’d put it in the nebuliser but it might be worth talking about the potential of Manuka honey with your son’s doctor. This field is changing all the time and I’m not actually a researcher within it :)

  11. Pam

    I am a 63-year-old librarian who has just been diagnosed with Brachiectasis with Pseudomonas Aeruginosa. Since you said that Manuka honey has anantibacterial on wounds, I began taking Manuka honey in my tea one or two times a day. From your previous post concerning CF, I am wondering if this is a good idea or not so good? Pam

    • Hi Pam,
      From what I have read my guess would be that it wont have much of an effect on your brachiectasis. That being said theres no reason to stop, personally I like honey in my tea :)

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