Sleeping bacteria evade antibiotics

27 June 2017

Interview with

Professor Nathalie Balaban, The Hebrew University

Across the world, bacteria are becoming increasingly resistant to the most commonly prescribed antibiotics. But resistance isn't the whole story. Bacteria frequently enter in periods of dormancy, when they effectively switch off. While they're in this state they stop being sensitive to the effects of many types of antibiotics. So even if they’re not resistant, they still might not be killed by a drug. And this can mean that infections keep coming back, so doctors end up using more antibiotics and that makes the resistance problem worse.

But to know how long the dormant spell is for a specific bug has always been hard to measure, and it’s certainly beyond the scope of most hospital microbiology departments. Now scientists in Israel have found a way to do this much more easily. Chris Smith heard how from Natalie Balaban, at the Hebrew University in Jerusalem...

Natalie - We actually discovered under the microscope that bacteria are able to survive antibiotic treatment, not only because they are resistant, but they have an alternative strategy, which is just to go dormant. If they are dormant they are going to survive the antibiotic treatment even if they are not resistant. So, if they wake up and the antibiotic is still there, that’s fine, the antibiotic will kill them because they are not resistant but, if they wake up after the antibiotic treatment has been stopped, the infection will go on.

Chris - In our present way of coping with, or managing infections in hospital or a general practice setting we don’t really consider the idea that different bugs might have different periods of dormancy, we just give a course of treatment and we assume that the bugs are going to die. But you’re saying we need factor in the fact that there will be dormant bacteria and we need to know how long that is for different strains of bugs and different infections?

Natalie - Exactly. Because these dormant bacteria can actually prolong the need of antibiotic treatment.

Chris - What have you done to get a handle on that previously intractable problem?

Natalie - The idea is to use statistical measurements. We put a small culture of 100 bacteria, we put on the antibiotic for different durations, and then we see which culture like that has survived the antibiotic treatment. By statistically analysing the results of whether they grew or didn’t grow we can know whether the bacteria can survive prolonged antibiotic treatment, and how long they can sleep under antibiotics.

Chris - How would that change clinical management? So, in a hospital setting a patient has a swab taken, we know they’ve got an infection, the swab would come to the laboratory. How would your technique affect the type of antibiotic the doctor would give, how long for, and how they would then manage the patient?

Natalie - When a swab is taken today, the hospital measure resistance and accordingly decide what antibiotic to give, and this is one number. We add another number which means how tolerant or how long the bacterium can sleep under different drugs. These numbers can direct the type of antibiotic that is maybe better than the initial choice without these numbers, and the duration of the treatment.

Chris - If you find there’s one particular strain of bug that you get from a patient and if you discover that has a very long dormant period, might you instead switch antibiotics altogether because it would be better to use a different antibiotic and, therefore, you minimise overall the exposure of the environment to more antibiotics?

Natalie - Yes, exactly. These dormant bacteria are better killed with other antibiotics that are less used than the common antibiotics that we use and, therefore, either changing the treatment would be the way to go if you have one of these sleeping bacteria in a patient, or the other way is to extend the duration of treatment.

Chris - What do you think the difference this could make would be? What’s the scale of the impact of what you’ve discovered?

Natalie - I think that what it can help is really tailor the antibiotic treatment to the properties of the bacteria that we have, and not only the property of resistance. It would enable us to extend the duration of treatment when needed and prevent relapse of all kinds of infections that we know are coming back after the patient’s stopped the treatment.

But, on the other hand, if you can test and see that the bacteria in one patient are actually not dormant and don’t have this property then you can shorten the duration of treatment.

Chris - So it’s not just about lengthening treatment, also it’s about reducing the overall use of antibiotics potentially - why use overkill if you don’t need to?

Natalie - Exactly, exactly.

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