How mobile are antibiotic resistance genes found in the environment?

Once we know that antibiotic resistance genes are widespread in the environment, there are two sorts of scientifically interesting questions that can be asked.

1. What are the resistance genes found in the environment?
2. How much of a threat do they pose to us humans?

Considerable work has already been done on question 1. This is a nice representative (and open access too!). The paper serves as a nice metagenomic systematic review if you will- it pools a large number of the metagenomes available in the databases, then aligns them against particular genetic elements databases which are directly or indirectly indicative of the presence of resistance genes. It’s basically like casting an iron net into a stack of hay containing the occasional magnets, then finding out which bits of the net stuck to which magnets. Maybe we could have a longer and less picturesque discussion on this some other day. In this blog post, I want to touch on question 2- although admittedly, I’ve just started reading about these topics and my views may very well evolve substantially.

The question of the threat of environmental isolates (=non-pathogens) bearing resistance genes boils down to whether their resistance elements can be shuttled off into human pathogens. If the resistance genes are transferable to pathogens, then that means the environment can act as a supply store for pathogens looking to get resistant. So how do we know if genes are “transferable” in this way from the environment to pathogens?

This review, based on the findings of these authors, propose two basic criteria.

1. If the resistance gene is surrounded by mobile genetic elements (aka jumping genes), then the region between the elements can jump off elsewhere. There are some truly intriguing molecular “jumping” mechanisms which I hope I’ll be writing about some day, but the point for now is- these mobile elements being present in the neighborhood of antimicrobial resistance genes indicate that the genes could be plausibly transferred.
2. High level of similarity between corresponding genes found in both types of isolates means there’s a (very) recent evolutionary relationship. So if you find two close to identical beta-lactamase genes in two sorts of isolates, it’s a safe bet to assume the element was transfered from one to the other.

Here’s the case study. The paper from Science I cited above compares a genetic region among a number of pathogens and a soil (environmental) isolate. This is how the comparison looks (taken from the Nature Reviews paper):

This picture captures both of the criteria I mentioned above.

First, in each of the sequences, the green bits indicate mobile genetic elements- meaning the blue and red resistance genes show potential of being shuffled off elsewhere.

More interestingly, not only does the non-pathogenic soil bacteria genome come with genes flanked with the green bits, but this particular gene order, to varying extents, shows up in the clinical isolates as well. Preservation of the order of genes in this way is called synteny. This indicates not only could the soil microorganism’s gene have been transferred, but it did in fact get transferred- only that can explain the precarious order of the genetic elements being preserved across all isolates.

Second, the blue shaded regions indicate regions of high (>99%) similarity. This too bolsters the earlier conclusion- if gene order weren’t enough, large parts of the sequences themselves have been near-perfectly preserved across both types of isolates.

These allow us to cumulatively infer not only the transferability, but the actual historical transfer of the resistance elements from the environment to the pathogens.