Germ genomes

04 November 2012

Interview with

Dr Matt Holden, Wellcome Trust Sanger Institute

Kat:: But now, it's time to take a closer look at bacterial genes. I spoke to Dr Matt Holden at the Sanger Institute in Cambridge to find out how advances in genome sequencing are helping researchers and doctors to understand more about bad bacteria, and even to track infections as they happen.

Matt:: Genome sequencing over the last say, 15 years of about bacterial sequencing has been very informative about having this amount of contents of a genome, and it's really propelled research forward. It allowed biologists and geneticists to have a glimpse of what the genetic blue prints of many important pathogens are and from that, try and dissect what are the important genes, what are the genes that allow it to survive in certain niches, what are the genes that maybe cause a damage when they're causing disease. In this case, we're now moving to a situation with sequencing where the technological advances of sequencing mean that rather than being a fundamental sort of research tool, which is sort of based in institutions like the Sanger Institute where I work and university labs, it's now been sort of transited to the sort of setting of a diagnostic lab because of the reduction in cost and increase in throughput.

So, we're now looking at genome sequencing as a diagnostic tool, so when you are identifying a bacteria, you won't just identify them by maybe culturing them on a selected media. You'll actually sequence the genome. So, for a pathogen that's been isolated from a disease situation, you can identify or reconstruct the genome and identify what genes it's carrying which can be very important when you're trying to provide information about what antibiotics to use because from the genome, you can predict what antibiotics the pathogen may be sensitive for. The key to this is, it can be done very cheaply or is certainly becoming cheaper and also, it can be done rapidly which means it can certainly provide clinicians and those involved in the management of disease, important information within a very short space of time.

Kat:: One of the things that you did recently was to actually track an infection, an MRSA infection. How did you go about doing that and what did you find?

Matt:: What we wanted to do was to use genome sequencing to look at the isolates that were identified in this outbreak that occurred on a neonatal intensive care ward and to see what information genome sequencing will provide that would help combat this sort of transmission in the future. So, we were also interested to discover what it told us about the outbreak itself or perhaps standard clinical diagnostics and infection control didn't. So we sequenced the genomes of 14 isolates that were identified as outbreak and also, additional isolates of MRSA that were identified in the hospital at the same time. And showed through genome sequencing, that we were able to effectively reconstruct a family tree for these bacteria.

So, what we were able to do was identify very clearly which bacteria are involved in the outbreak and showed that these were very distinct from the other bacteria that were floating around in the hospital at that time. But we're also were able to go into the genomes and predict what antibiotics the microorganisms were sensitive to. So, providing information that clinicians could potentially use very quickly to treat patients who are becoming infected and also, predict which toxins they were carrying which again, can be important to inform clinicians as to how to manage disease when it occurs in a clinical setting where you have potentially pathogenic bacteria that have got important toxins involved that can cause particular types of disease.

Kat:: How do you think being able to track the genetics of bacteria in this way will be useful to doctors and beneficial to patients in the future?

Matt:: Well obviously, the study we've done recently is very much a sort of proof of principle and so, it's a case where we're seeing what the potential of it is. Obviously, with technology changes, with technology progress, the cost of sequencing will go down and also, the rapidity with which you can sequence the genome is going to go up. So, the immediate benefit will be hopefully that you will be able to identify what bacteria is associated with infection, and whether or not it's related to other bacteria that part of an outbreak very rapidly, hopefully quicker than standard techniques. And also, with the decreasing cost, you can do it more cheaply.

The other benefit is you have the entire genome sequence there, so you can actually look at all the contents and provide all this additional information that we currently don't have. We get these extra resolution and be able to distinguish related bacteria, but we also get all the genetic information and it gives us a new insight to what the bacteria are carrying.

Kat:: That was Dr Matt Holden from the Wellcome Trust Sanger Institute.

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