Friday, October 17, 2008

The Origins of Antibiotic Resistance

ResearchBlogging.orgAntibiotic resistance is becoming an increasingly important plight that we face in our treatment against bacterial infections. The acronyms MRSA and XDR-TB have become headlines across the world; and the number of untreatable infections is on the rise. But even as we learn more about the increase in antibiotic resistance and what we must do to overcome this, we must also look into past evolutionary history and try to deduce how these resistance mechanisms arose.

One way to do this is to look for functional antibiotic resistance genes in a bacterial population that has not been exposed to our medical treatment pressures. Researchers from the University of Wisconsin-Madison recently published an article that shows just this. They have demonstrated that antibiotic resistance genes (specifically those which encode beta-lactamases) can be found in soil bacteria from pristine regions of Alaska. The Bonanza Creek Forest. Credit:

Using soil cores from a region of Bonanza Creek Experimental Forest, the researchers extracted bacterial DNA. This was then cloned into a library and constructs were screened for resistance to beta-lactamase. Those constructs that were positive for resistance were then subjected to transposon mutagenesis to identify the precise region conferring resistance.

Not only does this demonstrate that beta-lactamases were present, but more importantly, it demonstrated that these genes were functional. This is a far leap up from merely metagenomic sequencing. A sequence may be able to tell you if a type of gene is present, but it can not tell you if it is functional. Furthermore, merely sequencing may hide the presence of a beta-lactamase that has no homology to known genes.

Of the nearly 12 Gigabases of DNA that they extracted, they isolated 14 clones that had the ability to grow on clinically significant concentrations of beta-lactam antibiotics. The genes encoded by these clones were found to be distantly related to the current bank of known beta-lactamases. This allows us to have a look back in time to see the functional beta-lactamases that gave rise to the types in our current strains.

(The authors also found the first example of a bifunctional beta-lactamase. That is, a single protein created by the fusion of two different, yet functional, beta-lactamases. Perhaps an example of duplication giving rise to a new subset?)

I am a firm believer in the fact that in order to know where we are going, we must always remember where we came from. On that note, in order to provide better answers to antibiotic resistance, we must first understand how it arose.

Allen, H., Moe, L., Rodbumrer, J., Gaarder, A., & Handelsman, J. (2008). Functional metagenomics reveals diverse β-lactamases in a remote Alaskan soil The ISME Journal, 3 (2), 243-251 DOI: 10.1038/ismej.2008.86

Other articles of interest:
Altruism in Bacteria? Allowing Yourself to Die for the Good of the Species
Wild Bacteria That Eat Our Antibiotics?! Of Course!