Peter Mullany – unveiling antibiotics resistance genes

A better understanding of the genes associated with antibiotic resistance may contribute to the development of rapid detection methods

Nowadays, doctors treat patients with broad spectrum antibiotics without testing. But if they want to test they can send the bacteria away to a laboratory. This microbiology laboratory will test sensitivities to antibiotics for them. Peter Mullany, who is a molecular microbiologist at University College London, UK talks to about his research on antibiotic resistance genes, under the EU-funded ANTIRESDEV research project. This will contribute to the development of new array-based solutions for near real-time detection of antibiotic resistance. These could reduce the detection time from a few days, down to a few hours.

What advantages to microarrays offer over standard laboratory tests?
They are much quicker than waiting for the bacteria to grow [through cultures].  Some bacteria take three or four days to grow, whereas I think microarrays will give an answer on the same day. 

What are the challenges that lie ahead before such an array could be used in hospitals.
It mostly involves refining the techniques, though the microarray part is not really what we worked on.  Our part of the project was to discover new antibiotic resistance genes that could be put on the arrays. So we need to make sure that all the antibiotic genes are covered. And we also need to find out all the ones out there.

A lot of these genes are on mobile genetic elements. They can therefore transfer to all sorts of different bacteria given the right selection pressures.  There are probably at least thirty or more that can resist just tetracycline [an important antibiotic].   We might be getting close to finding all resistance genes, because we did not find many new ones.  But new combinations are always being found—there is probably an infinite number of those.

Any notable findings in the project from your own lab?
Some of these genetic elements can only move in narrow species of bacteria. And some can travel between great numbers. One thing we found was an antiseptic resistance gene linked on the same genetic element as an antibiotic resistance gene. That means there is a possibility that if you are swabbing down with that antiseptic you are also selecting for antibiotic resistance, so that was quite a new finding.  The antibiotic was tetracycline.

What happens to a patient’s own microorganisms when you give them an antibiotic?
A lot is unknown about that.  One of the reasons for that is the majority of organisms still cannot be cultured. It is not really known what effect antibiotics are having on the non-cultured faction of the microbiota.  This metagenomic approach that some of the project partners were using gives us some more info about this effet. This allows us to find out what is happening about the whole microbiota, rather than just the cultivable part. 

What does the metagenomics approach consist of?
Metagenomics is really getting hold of the microbial DNA from an ecosystem. You can sequence certain genes within that metagenome, which tells you the proportion of different bacteria present, even ones that have never been cultivated before. So we just get hold of the DNA, there is no need to grow any of the organisms.

Ultimately how will this project help patients?
If you can get rapid knowledge about what antibiotic genes are present, and if you find out no antibiotic resistance genes are present to an antibiotic you want to use, there is a good chance the treatment will be successful and that you are not selecting for the spread of resistance. And likewise, if there are any resistance genes present the treatment might fail. You need to choose a different antibiotic.

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