Sunday, May 17, 2015

A Look Into The Viruses That Control Your Stomach Bacterial Infections (Including Probiotics)

Microscopy image of Enterococcus. <SOURCE>
Biofilms continue to be hugely significant problems when treating bacterial infections. Biofilms are groups of bacteria that stick together and to a surface while surrounding themselves in a thick extracellular matrix. You can think of this as the collective bacteria sticking to a surface like a slimy ball of goo. These are very serious infections because the bacteria adhere very tightly to the surface (which could be your bone, a catheter, or your wounded tissue), and antibiotics often have a difficult time penetrating the thick mucous matrix. This means the bacteria are particularly hard to kill.

Biofilms have five phases of development, as you can see in the figure below. The bacteria attach to the surface (phases 1 and 2) and proceed to multiply, thereby contributing to growth of the biofilm (phases 3 and 4). Once the biofilm has grown and matured, some of the biofilm bacteria are released to travel to new substrates and establish new biofilm infections (phase 5). Often this dispersal is mediated by quorum sensing molecules, which are molecules used by bacteria to sense the presence of other bacteria, as well as the population size of the bacterial community. Put plainly, a single bacteria knows there are a lot of other bacteria present in the community when the quorum sensing molecule concentration is high in the environment.
Five stages of biofilm development: (1) Initial attachment,
(2) Irreversible attachment, (3) Maturation I,
(4) Maturation II, and (5) Dispersion.  <SOURCE>
A couple of months ago a research group led by Rossmann et al published a report describing a role for bacteriophages (bacterial viruses) in quorum sensing mediated biofilm disruption. As if that was not cool enough, they also went on to illustrate the roles of these phages in promoting the distribution of virulence genes (the genes bacteria use to make you sick) among other bacterial communities. In this post, I want to briefly go over the findings from this paper, and more importantly, how this might affect the way we think about the roles of phages in the gut microbiome.

The study focused on Enterococci, which are gut commensals (meaning they harmlessly live with you all the time) as well as very serious potential-pathogens that can cause very severe biofilm infections. The research group showed these bacteria do in fact produce, and are sensitive to, the AI-2 quorum sensing molecule. The presence of AI-2 on an Enterococcus biofilm indeed caused disruption of the biofilm, which affects phase 5 of the biofilm formation as discussed above. Interestingly, the group used both RNA-sequencing and molecular techniques to show that this Enterococcus biofilm dispersion was mediated by prophages that were integrated into the bacterial genomes, and that this dispersion could not occur without the prophages. This is really important because it provides us with further insight into how these pathogenic bacteria infect humans, and because it further illustrates the crucial roles phages have in bacterial virulence.

Bacteriophages, like this one infecting a bacterial cell, can
transfer virulence genes and make the bacterial host
pathogenic. <SOURCE>
Not only do the phages play an integral role in dispersal of the bacterial biofilm so that the bacteria can move to infect other sites, the phages also spread bacterial virulence themselves by carrying virulence genes to other bacteria. Rossmann et al used a seemingly harmless probiotic strain of Enterococci to drive this point home. In short, the group found that exposing the harmless probiotic bacterium to the free bacteriophages from the pathogenic strain of Enterococci allowed the phages to integrate into the probiotic genome. This integration allowed the previously harmless probiotic bacterium to act like the original pathogenic bacterium by responding to biofilm quorum sensing and overall act more like the pathogenic strain. Both in vitro and in vivo mouse studies suggested that the phages indeed made the probiotic strain more virulent by providing it with virulence genes. Overall, the results suggest that the phages are indeed able to transform a harmless probiotic bacterium to a more virulent bacterial strain.

This paper is super interesting because it really highlights the roles for bacteriophages in bacterial pathogenesis, virulence, and infection. These findings are particularly important to the microbiome field where we are very interested in the medical benefits of probiotics, prebiotics, and fecal microbiome transplants. One question that came to mind while reading this study was how commensal phages might be impacting administered probiotics? Additionally, what kind of phage screening might we see in the future as we use more and more fecal microbiome transplants? I am not saying that these therapies are dangerous because of bacteriophages, but I want to highlight these important questions and the fact that phages certainly play complex roles in bacterial pathogenicity and our health. Of course, further research is going to be needed to tease this apart further, so we will have to stay tuned.

For the whole story, feel free to check out the paper. It is open access, which means anybody can access and read it. It is actually a pretty straightforward read so definitely check it out. Additionally, always feel free to drop me a comment below with any questions, comments, or opinions about the topic I covered above.

Works Cited

Rossmann, F., Racek, T., Wobser, D., Puchalka, J., Rabener, E., Reiger, M., Hendrickx, A., Diederich, A., Jung, K., Klein, C., & Huebner, J. (2015). Phage-mediated Dispersal of Biofilm and Distribution of Bacterial Virulence Genes Is Induced by Quorum Sensing PLOS Pathogens, 11 (2) DOI: 10.1371/journal.ppat.1004653

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