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Understanding antibiotic resistance
Understanding antibiotic resistance

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3.1 Treating infections with Bdellovibrio bacteriovorus

In the next activity you will look at some recent research that uses Bdellovibrio bacteriovorus to treat infections in an experimental model.

Activity 5 Treating infections with Bdellovibrio bacteriovorus

Timing: Allow about 15 minutes

Listen to the following audio clip from the BBC’s Inside Science programme. Liz Sockett from the University of Nottingham talks about research using Bdellovibrio bacteriovorus to treat Shigella infections in zebrafish. You may also like to watch Video 2 which shows a Bdellovibrio bacteriovorus bacterium (labelled in red) preying on a Shigella bacterium (labelled in green) inside a zebrafish larva.

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Transcript: Audio 2 Interview with Liz Sockett about research with Bdellovibrio bacteriovorus.

INTERVIEWER:
Using one organism to kill another might not seem like such a great idea, but cats do make very good ratters. Scale things down a bit, and we might just be able to use one bacterium to kill another. Shigella is a family of bacteria that causes dysentery, and hundreds of thousands of deaths, mostly children, every year. Now good sanitation prevents Shigella infections, but there is no vaccine that stops it.
Enter Bdellovibrio bacteriovorus. It's another type of bacteria, but crucially, it's a predatory one. It inserts itself inside its victims and then destroys them from within. And a new paper just published shows that Bdellovibrio can be used to cure a Shigella infection, admittedly in zebrafish, but with no apparent side effects.
And because these bacteria attack a wide range of other microbes, this might just be a way of treating the impending antibiotic resistance crisis. Elizabeth Sockett is the woman behind this study. And I asked her how the experiment worked.
ELIZABETH SOCKETT:
The experiment's a real synergy between two labs. So Serge Mostowy's lab could set up experimental infections into zebrafish with the Shigella. And in our experiments, the Shigella were green fluorescent. They're injected into the hind brain of the zebrafish. Normally, they cause a lethal infection and the zebrafish die. What we did was we injected red Bdellovibrio into the same compartment. And we tested whether those red Bdellovibrio or a buffer control could change the infection.
So the great thing about this experiment was we could see live the numbers of red and green bacteria changing inside the patient, who's the zebrafish. We could also measure the survival of the zebrafish 48 hours later, because they normally die of a Shigella infection of that level. And what we saw was that the red Bdellovibrio started to kill the green Shigella inside the zebrafish, and the survival of the zebrafish improved a huge amount.
INTERVIEWER:
So you inject, first of all, you infect the zebrafish with Shigella, which would kill them.
ELIZABETH SOCKETT:
Yes.
INTERVIEWER:
Then you inject--
ELIZABETH SOCKETT:
With the Bdellovibrio.
INTERVIEWER:
And that kills the Shigella.
ELIZABETH SOCKETT:
Yes. And interestingly, in this experiment the Bdellovibrio start killing first the Shigella, but then the immune system of the fish that wasn't coping with the Shigella wakes up and gets a stimulus from this predation. And it comes in and clears up the rest of the Shigella from the infection. So what we think is that the Bdellovibrio is actually releasing some components of the Shigella as it's killing them early on and the immune system is being awakened to the presence of the Shigella. And also the numbers are dropping due to the direct killing by the Bdellovibrio.
End transcript: Audio 2 Interview with Liz Sockett about research with Bdellovibrio bacteriovorus.
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Audio 2 Interview with Liz Sockett about research with Bdellovibrio bacteriovorus.
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Video 2 Predation of Shigella by Bdellovibrio bacteriovorus inside a zebrafish larva (Willis et al., 2016).
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Using the information in the interview, complete the following statements about the experiment described by Professor Sockett. The missing words are given below to help you.

Bdellovibrio bacteriovorus

Shigella

Zebrafish

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Answer

a) Zebrafish were used as the host for the infection.

(b) Shigella infections are normally lethal for zebrafish.

(c) Bdellovibrio bacteriovorus preys on Shigella, killing them and stopping the infection.

(d) As well as killing the Shigella bacteria directly, Bdellovibrio bacteriovorus stimulate the host immune system to help clear the infection.

Now listen to another clip from the same interview in which Professor Sockett discusses how Bdellovibrio bacteriovorus could be used as a treatment and the advantages that this treatment might have.

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Transcript: Audio 3 Interview with Liz Sockett about Bdellovibrio bacteriovorus.

INTERVIEWER
Some of the press have picked up on this study and this paper and reported it as being this might be a way to address the big problem with antibiotic resistance. Do you think that that is a plausible channel?
PROFESSOR SOCKETT
So I think this could be good for injected antibiotic resistance clearance at sites in the body. At a surgical site- so if there's an infected wound site- we might inject the Bdellovibrio into that position in one site in the body, rather than necessarily take it into the gut. This won't be like a drug where you take it orally and it spreads throughout the whole of your body and removes bacteria at all different sites. But because these Bdellovibrio are alive, and because they do tackle antibiotic-resistant bacteria naturally, they can change as the antibiotic-resistant bacteria change. So it's a living therapy.
INTERVIEWER
And does that get around the possibility that the bacteria they're attacking, such as Shigella, might develop resistance to Bdellovibrio in the first place?
PROFESSOR SOCKETT
Yes, because if, say, there is a resistant strain, you could always co-culture it in the lab with Bdellovibrio and select for Bdellovibrio that get around the resistance it develops. But the Bdellovibrio themselves use hundreds of enzymes to degrade the bacteria. So it's not like a drug with a single target, it's a system of lots of different methods. It's like having lots of weapons and using them all at once on the pathogen. So that's a good thing.
End transcript: Audio 3 Interview with Liz Sockett about Bdellovibrio bacteriovorus.
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Audio 3 Interview with Liz Sockett about Bdellovibrio bacteriovorus.
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Note down in the table below any differences between a potential Bdellovibrio bacteriovorus treatment and antibiotics that Professor Sockett mentions in the audio clip.

Bdellovibrio bacteriovorusAntibiotics
Type of treatment
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Likelihood of resistance arising
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Tackles antibiotic-resistant bacteria
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Words: 0
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Answer

Bdellovibrio bacteriovorusAntibiotics
Type of treatment Local injection at site of infection, e.g. a wound Systemic – taken orally and spreads throughout the body to treat infections at many sites
Likelihood of resistance arising

Low – living treatment so can adapt as the infectious pathogen changes

Uses many enzymes to kill the bacteria, rather than one specific target, so resistance would require many changes in the infectious bacteria

High – one mechanism of action so may require a single change in the bacteria for resistance arise
Tackles antibiotic-resistant bacteriaYesNo (depending on whether the bacteria are resistant to the prescribed bacteria)