Surprise Attack - Stopping Bacteria from Sensing your Immune Response

21 September 2008

Interview with 

Vanessa Sperandio, Southwestern Medical Centre, University of Texas


Chris - Some bacterial infections, like E. coli 0157 which is a cause of food poisoning  and can also damage your kidneys, seem to get a lot worse when you give patients antibiotics, instead of getting better.  It seems that this is because the bacteria enter a sort of high-alert state in response to the treatment.  They fight back by becoming a lot more virulent.  Researchers at the Southwestern Medical Centre, University of Texas have come up with a drug that can stop the bacteria from sensing the chemicals in your body that tell the bacteria your body's gearing up to fight them.  Dr Vanessa Sperandio is in Dallas and she joins us to tell us a bit about this research.  Hello...

Vanessa - Hello Chris.

E. coli 0157Chris - How do bacteria home into the fact that we're on to them?

Vanessa - They sense two stress hormones that you have: adrenaline and noradrenaline, and they use those two hormones as cues to know they are inside of you.  When they sense that through a receptor in the bacteria they activate production of the virulence trait.  By doing that they can actually make you sick and turn on everything that will cause disease.

Chris - It's intriguing to think that these bacteria are eaves-dropping on our own inflammatory signals.  They've learned or evolved, I should say, to detect the signals our body uses to fight them.

Vanessa - Yes, and those are very primal types of signals.  That's at the core of your immune system and it's the core of gauging how well - how healthy or not you really are and how stressed you are.

Chris - How did you get a handle on what the bacteria were doing and then try to work out how to stop them?

Vanessa - We figured out many years ago that they were using the signals and then in 2006 we were able to identify one of the bacterial receptors for this signal.  What we've done now is to develop drugs that will bind to the bacteria receptors and prevent the receptors from seeing the host's stress hormones.  In this way the bacteria passes blindly through the host without being able to know where it is and activate it virulence traits.

Chris - So you've managed to come up with a drug molecule that can block up the ability of the bacteria to see adrenaline or noradrenaline so the bacteria don't effectively know they're in the body.

Vanessa - Yes.

Chris - How could this molecule be used and is it safe?

Vanessa - So far the molecule is safe.  Of course, this is in the lab of proof of principle.  We did do some preliminary toxicology in mice and so far it looks to be safe.  It also does not signal to human adrenergic receptors, which is important.  It can be used either to treat infections or hopefully we want to try to use this to prevent infections.

EpinephrineChris - Which sorts of bacteria will be vulnerable to this?  You've done tests on a number of different classes of bacteria but where do you see it actually being most useful?

Vanessa - It can be very useful for something like E. coli 0157 which, right now, has no treatment.  We also did look at this drug to treat salmonella infections which can cause gastroenteritis and typhoid fever.  We looked into tularaemia which is a bioterror agent.  In between these bacteria there are several important pathogens that have this sensor.  This could be used hopefully to treat some of the communal infections especially for patients in ventilators.  Bacteria like klebsiella, acinetobacter, pseudomonas who are important in this class of patient'swhich do not have a lot of treatments and antibiotics against and are quite resilient to the biotic treatments.  They all posses this signalling system.

Chris - When do you think that we might be seeing this going into humans in clinical trials?

Vanessa - We've got money from the National Institute of Health to develop this drug to pre-clinical in five years which means in five years we want to be able to have everything pre-clinically, toxicology and safety done.  Hopefully in five years we'll start the first safe trials in humans.

Chris - Thank you Vanessa.


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