Wednesday 18 December 2013

PHAGE THERAPY FOR TREATING A CORAL DISEASE

          Phage therapy means using bacteriophage/phages capable of killing the bacterial pathogens, for treating the disease caused by that bacterial pathogen. Using this method of disease treatment has a number of benefits such as particular phage specifically target bacterial pathogen and other bacteria (including beneficial associated microbes) remain unaffected, as density of bacterial pathogen decreases, consequently phage concentration also declines. The same authors have previously reported isolation and characterisation of lytic phages for two bacterial pathogens of corals. This study particularly looked at treatment of white plague-like (WPL) disease in a coral species Favia favus, caused by a bacterium Thalassomonas loyana.
          
        Field experiments were conducted in the Red sea of Eilat, Israel. The study was conducted by injecting phage BA3 (capable of infecting specifically T. loyana) to the treatment which was compared to controls which were without the dose of phage. The experiments were conducted for two times, firstly in 2009 and then in 2011. Corals from these treatments were transferred in aquaria and divided as per their healthy/diseases status. Phage concentration in these aquaria waters was measured by soft agar overlay technique. Coral samples were prepared and used for identification of T. loyana by 16S rRNA gene sequencing.
          
      The authors noted little reduction in the living tissue in the phage treated corals whereas in the non-treated controls, living tissue was significantly reduced along with the mortality of few diseased corals. They also noted that phage treatment also significantly reduced transmission of WPL disease.

If phage therapy is to be operated on a large scale for treating coral diseases, developing a technique for delivering phages to infected corals over a large area, production of sufficient phages for treating large area of a reef and convincing local authorities for safety of this therapy by providing necessary evidence, would be required. Regarding concentration of phages required for treating the disease, authors showed that 103 phage per ml (which is a thousand times higher than their natural abundance in Eilat seawater) is enough to prevent the spread of WPL. Extrapolating these figures, the authors suggested that production of sufficient phages to treat a large area of a reef is possible. Nevertheless, authors did not address issues such as feasibility of phage therapy on reefs, in terms of its costs and effectiveness. Similarly, they did not address any limitations of it. A limitation which I can think of is its applicability to only few bacterial diseases which are caused by a single bacterial pathogen, but what about diseases like black band disease which is caused by a consortium of pathogens?

This study proves that phage BA3 can be effective against progression and transmission of WPL disease. Interestingly, as BA3 phage can only infect T. loyana; this study also confirms that T. loyana is the causative agent of WPL disease. This discovery led authors to suggest that in nature, phages may be playing a role in making few of the corals naturally resistant to certain bacterial diseases, which I found thought provoking. As authors suggested, perhaps, this is why many times healthy corals are surrounded by diseased corals. Could the phages of Vibrio shiloi have played any role in making the coral Oculina patagonica resistant against V. shiloi? The authors could have discussed this idea of “can phages confer resistance against bacterial pathogens?” in the context of coral probiotic hypothesis and hologenome theory of evolution. The discussion of this paper is very short and I think it is incomplete. I think this is a revolutionary idea that phages could play a role in providing natural resistance to organisms against bacterial diseases. How widely applicable this idea would be? Could we link it to natural resistance of few individuals to a bacterial disease epidemic of humans and other animals?


Atad, I., Zvuloni, A., Loya, Y., & Rosenberg, E. (2012). Phage therapy of the white plague-like disease of Favia favus in the Red Sea. Coral reefs, 31(3), 665-670.
                            



5 comments:

  1. How is it known that BA3 phage only infects T. loyana? Isn't it conceivable that it may infect other bacteria that haven't been tested for? It is a worry that in trying to biologically control one thing, that we induce a problem elsewhere.

    ReplyDelete
    Replies
    1. Hi Rachel,

      Thank you for commenting.
      So, regarding your concern, the authors of this paper have clearly described in their "introduction" the benefits of phage therapy which include "host specificity" and "environmental safety". The authors have said that by citing
      “Duckworth DH, Gulig PA (2002) Bacteriophages: potential treatment
      for bacterial infections. BioDrugs 16:57–62.” If you need more information about environmental safety of phage therapy, you may see this paper.
      Again in the introduction, the authors have clearly stated “the phages only attacks and destroys the specific pathogen, leaving the remaining beneficial microorganisms untouched” by citing “Weld RJ, Butts C, Heinemann JA (2004) Models of phage growth and their applicability to phage therapy. J Theor Biol 227:1–11.”

      Now speaking strictly about T. loyana, the same authors have studied BA3 bacteriophage in detail (with its genome fully sequenced) and have tested pattern of its infection in T. loyana and its potential to treat T. loyana caused white plague like disease in coral. This previous study was published in 2009. Here is citation of the paper – Efrony R, Atad I, Rosenberg E (2009) Phage therapy of coral White Plague Disease: properties of Phage BA3. Curr Microbiol 58(2):139–145.

      I hope this satisfies your worry.

      Delete
    2. Thanks Sanket. For me, introducing biological solutions into the wild will always be a big concern - once it's done, it's practically impossible to undo. Sometimes we think we've covered all the bases, then something happens that we haven't thought of and it's too late!
      Don't get me wrong, I think it's a great concept, but we just don't know all the potential variables that may affect this over such a large scale and in the long term.

      Delete
  2. I agree with you Rachel; the treatment sounds like a good solution for preventing the infection of corals and the spread of this specific disease, however, I think that introducing an unnaturally high amount of these viruses into the ecosystem could have great impacts on other important bacteria. How can they be sure that only the White Plague-causing strains are affected by this and not any other bacteria that are potentially important to the corals or other animals? Although your references are very certain that these phages are species specific, how can they have tested every single bacterial species in this environment? Moreover, viruses are known to show rapid mutation in some cases so there is also a possibility that the viruses also attack other bacteria and not just the previously targeted ones.
    I understand that phage therapy could offer a great solution for the spread of coral disease, yet I think that it's not a good idea to introduce them in unnatural amounts into the environment.

    ReplyDelete
    Replies
    1. Rachel & Malin, both of your critique on phage therapy definitely needs to be considered. I agree with what you both think and I appreciate that.
      But you may also think from this side – every coin in this world has two sides. I mean, everything in this world has positive and negative sides. There is nothing which has only benefits or plus points. You will always find some shortcomings or drawbacks in everything. For example, think about antibiotics. How happy everyone was when antibiotics were discovered for first time. Scientists of that age used to think, “We have conquered infectious diseases.” But now all of us are aware how bad antibiotics can be and where they might take us in future (most of all pathogens would be resistant to all know antibiotics?) Malin and Georgia have recently reviewed papers that are alarming us about antibiotics use.
      In a possible future or current scenario, when we would no longer be able to use antibiotics at all (In case of treating coral diseases we can never use antibiotics at all, anyway) we would be left with only two options - trying to resolve disease epidemic by using available, (apparently) safe treatments like phage therapy or witnessing coral reefs dying and getting destroyed in vain. In such case, as a last resort, we may go for solutions like phage therapy, what else we could do?
      But certainly, further research is needed in future to see if there are any environmentally detrimental impacts (including any impacts on other microbes) of phage therapy. Secondly, we also need to think, would we really ever need to treat bacterial epizootics of an ecosystem like coral reef? Coral holobionts might find their own ways to get resistant against their pathogens, with the help of their dynamic microbial consortium as proposed in coral probiotic hypothesis and hologenome theory of evolution. This is why; I have said in my blog post that the authors could have put these issues in their discussion. The discussion of this paper is very short and (according to me) is incomplete. They have also not discussed any possible limitations of phage therapy which I’ve also included in my post, above.

      Delete