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Storify of #Microtwjc Christmas Edition

This time (18.12.2012 at 8 pm British Time) the Journal Club will be on a publication on the origin of antibiotic resistance:

I have chosen this paper because it is a topic of public interest and rising awareness on how resistance actually arises and works might help in understanding it in a broader sense. And because it is yet another example that nature has it all, we just have to bother looking for it. 🙂

On the one hand there are arguments and data supporting the theory that the very presence of antibiotics by the use in farming and medicine is the major factor for the appearance of resistance to antibiotics. On the other hand this publication shows that microorganisms sampled from an isolated cave, without contact neither to the surface nor to human influence, show resistance to  current antibiotics on the market. Nevertheless it seems as if both factors are playing an important role in the development of resistance.

The researchers from G. Wrights lab in Hamilton, Canada sampled three different sites of the Lechuguilla Cave (New Mexico, USA) in its most isolated regions (no contact to the surface or humans for 4 million years) and ended up with 93 isolated strains of which 33% were gram negative and 63% gram positive. The bacterial species were identified by 16s rRNA sequencing and were then screened on their resistance towards 26 different antibiotics. After a first screen, the MIC was determined for the positive results as well as testing if an inactivation of the antibiotic had occurred. The researchers also characterised a macrolide kinase from B. paraconglomeratum, which  was one of the isolates that could enzymatically inactivate erythromycin and its semi-synthetic derivative telithromycin. The motivation of this was that the phosphorylation of macrolides is a growing problem in clinical environments. The enzyme from the cave isolate was compared to a surface bacterium of the same genus B. faecium.

Furthermore they discovered two new mechanisms of resistance previously unknown: daptomycin hydrolysis and a macrolide phosphorylation by a MPH class antibiotic kinase (from B. paraconglomeratum).

The authors state, even though the sample number was relatively low, the study nevertheless, points towards the richness of the natural reservoir in “untouched” areas. It is probably not only a source to understand antibiotic resistance found in non-pathogenic bacteria, but also for the discovery of new compounds.

There are some articles from newspaper/National Geographic online about this publication (there are even more under this link, if you are interested ):

Discussion points:

How was the publication written?

Do you think this pulication gives useful data/arguments to the discussion about the origin of antibiotic resistance?

Would you have liked to see any other experiment?

The storify transcript can be found at: Transcript for week 16

Following on from our discussion on Tues 4th Dec the transcript was passed on to the authors of the paper. We received the following response. The #microtwjc team would like to thank them for providing us this feedback. Enjoy….

Response from Authors

It was fantastic to see that our recent paper (Blower TR, Evans TJ, Przybilski R, Fineran PC, Salmond GPC (2012) Viral Evasion of a Bacterial Suicide System by RNA-Based Molecular Mimicry Enables Infectious Altruism. PLoS Genet 8(10): e1003023.) was selected as the topic for discussion in #microtwjc Week 16. After scanning the content of the discussion, the overall impression of the paper seems to be quite good (to our relief!). It is really great to see that more people are getting interested in, and excited about, bacterial viruses. There is certainly plenty to get excited about – they are the most abundant biological entities on the planet, after all!

There were a couple of points that arose which can be cleared up. Yes, the escape phages were selected first – as independent isolates – and then sequenced. The only mutations we found were in the “escape locus” (and hence that’s the reason for the close-up of this section in Fig 3 rather than present meaningless and redundant whole genome alignments). The transduction experiments we described allowed us to demonstrate that the the phages had the capacity to perform horizontal gene transfer of the phage-resistance mechanism. This was a nice observation, but we did try to avoid the temptation of over-interpreting this result in the paper, as we considered it more appropriate for the reader to perhaps extrapolate from the data (although, we hope that we may have a little more information on this front in the future!!!).

The final very interesting point that came up in the comments was whether or not these escape phages might exist in nature – or are they just a bizarre lab artifact? Obviously, given that we could see the evolution of this behaviour under lab conditions, by definition this confirms the potential for escape phages to arise in this fashion in the natural environment. Ultimately, this is a numbers game and we know that there must be a phenomenal abundance of bacteria-bacteriophage interactions occurring in the natural environment. So it is at least formally possible that escape phages like ours certainly do exist already (a stunning statistic that might help to illuminate the point is that there are thought to be around 10^25 phage infections happening per second on Earth (Lima-Mendez G, Toussaint A, Leplae R (2007) “Analysis of the phage sequence space: The benefit of structured information”. Virology 365:241-249)). The difficult conundrum of trying to find these (presumably rare) pre-existing phages is that, by definition, they are already resistant to the system and so cannot be readily distinguished using this as a facile selection method (in comparison with the enormous numbers of phages that simply naturally “ignore” this particular abortive infection system anyway). Instead, it would have to be a blind bulk sequencing search. That’s possible with recent technologies, but a little long-winded (and potentially pricey!). Hope that helps to explain these last points.

Thanks again to everyone who took time to read the paper and get involved in this discussion. That was much appreciated by the group. We were impressed by the engagement you all showed and we were really happy that you found the paper interesting and worth the time and effort involved.

Remember – All the world’s a phage!.