It's a neat paper that focusses on characterising the levels and kinds of antibiotic resistance in bacteria that live in a relatively isolated cave in New Mexico that has had extremely minimal human contact. The major point of this paper is that compared to other studies their site seems to be the most isolated microbial community, although this investigation in Alaska may be just as isolated. Although I dont think they can rule out water contamination from outside the cave system (actually from reading this article in NatGeo I think they can rule that possibility out). This they say is an 'ideal ecosystem' to study the original antibiotic resistance programs in the absence of human exposure.
To do this they employ a culture dependant approach, so obviously will only detect a small number of resistant microbes yet may be able to detect resistance mechanisms that we did not know about and so could not easily detect through purely molecular means. They do even find completely new ways that microbes have evolved to handle antibiotics.
One perhaps good thing about their results is that this cave is isolated so perhaps woudn't be such a reservoir for novel antibiotic resistance genes in a clinical setting.
A statement from their conclusion explains:
Antibiotic resistance is manifested through a number of different mechanisms including target alteration, control of drug influx and efflux, and through highly efficient enzyme-mediated inactivation. Resistance can emerge relatively quickly in the case of some mutations in target genes and there is evidence that antibiotics themselves can promote such mutations [43], [44], [45], [46]; however, resistance to most antibiotics occurs through the aegis of extremely efficient enzymes, efflux proteins and other transport systems that often are highly specialized towards specific antibiotic molecules. Such elements are the result of evolution through natural selection; this therefore implies that antibiotic resistance has a long evolutionary past.
and
The remarkable genetic diversity of the antibiotic resistome, uncovered in this and other studies has additional practical application as an ‘early warning system’ for new drugs introduced into the clinic. Resistance mechanisms in the environmental resistome can emerge in the clinics and the clinical community should be aware of them...
Some questions I had are:
How isolated is this community?
Would it have better (possible?!) to sequence everything?
Should we be worried about this resistance?
If not effected by human antibiotic use, why do they have resistance mechanisms?
Antibiotic Resistance Is Prevalent in an Isolated Cave Microbiome
Antibiotic resistance is a global challenge that impacts all pharmaceutically used antibiotics. The origin of the genes associated with this resistance is of significant importance to our understanding of the evolution and dissemination of antibiotic resistance in pathogens. A growing body of evidence implicates environmental organisms as reservoirs of these resistance genes; however, the role of anthropogenic use of antibiotics in the emergence of these genes is controversial. We report a screen of a sample of the culturable microbiome of Lechuguilla Cave, New Mexico, in a region of the cave that has been isolated for over 4 million years. We report that, like surface microbes, these bacteria were highly resistant to antibiotics; some strains were resistant to 14 different commercially available antibiotics. Resistance was detected to a wide range of structurally different antibiotics including daptomycin, an antibiotic of last resort in the treatment of drug resistant Gram-positive pathogens. Enzyme-mediated mechanisms of resistance were also discovered for natural and semi-synthetic macrolide antibiotics via glycosylation and through a kinase-mediated phosphorylation mechanism. Sequencing of the genome of one of the resistant bacteria identified a macrolide kinase encoding gene and characterization of its product revealed it to be related to a known family of kinases circulating in modern drug resistant pathogens. The implications of this study are significant to our understanding of the prevalence of resistance, even in microbiomes isolated from human use of antibiotics. This supports a growing understanding that antibiotic resistance is natural, ancient, and hard wired in the microbial pangenome.
This is absolutely unsurprising. Bacteria have been using antibiotics as warefare against one another for many many millions of years. It's so egoistic of us to think antibiotic resistance evolved in response to our use of antibiotics. After all...we got our first (and still get many of them) from the organisms that make them!
ReplyDeleteWhat the hell!?!?!
This paper provides one of the very few examples of actual hard evidence for that theory. That's why I think it's such a neat paper.
DeleteConcerning the overall message of the paper, I am frankly not surprise and our Anonymous colleague said. After working ofr several years with a formidably resistant opportunistic pathogen that leaves just almost everywhere, it has become pretty clear that antibiotic resistance is a fact if daily like for microbes when dealing in any ecosystem. My suggsted answers to your questions are:
ReplyDeleteHow isolated is this community?
For isolation, I assume, you refer to access to medically relevant antibiotics. I think this is irrelevant, The question should be, what is in the environment of these population
Would it have better (possible?!) to sequence everything?
Perhaps, but the point to make was the there were antibiotic resistance genes despite the old age of the community.
Should we be worried about this resistance?
No ore than any other.
If not effected by human antibiotic use, why do they have resistance mechanisms?
You meant "affected", and also human antibiotic use plays a minor fraction of the extent of antibiotic resistance. As said before, think of a bacterium living in contacts with other bacteria, lichens, actynomycetes, fungi. What do you think these creatures made and release around?