Podcast: Persistent antibiotic resistance, and modelling hot cities

Host: Benjamin Thompson

Welcome back to the Nature Podcast. This week: hidden antibiotic resistance in Salmonella...

Host: Nick Howe

And cities feeling the heat. I’m Nick Howe.

Host: Benjamin Thompson

And I’m Benjamin Thompson.

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Interviewer: Benjamin Thompson

First up on the show, I’ve been finding out about Salmonella bacteria lying in stasis and how they could be a hidden source of antibiotic resistance. In this case, we’re talking about Salmonella Typhimurium – a type of Salmonella that can cause nasty bouts of food poisoning. It’s a common infection, with millions of people getting it each year. Now, when this bacterium gets into someone’s gut – perhaps via an undercooked burger – it has to compete with the person’s gut bacteria for nutrients. If it’s able to gain a foothold in the centre of the intestine, the space known as the lumen, the infection can progress, as Wolf Hardt from ETH Zurich in Switzerland explains.

Interviewee: Wolf Hardt

Once it has achieved this, it starts to invade into gut tissues and this tissue invasion is causing a response of your gut’s immune system that tries to protect you, but in principle, this is causing the disease symptoms that you then experience.

Interviewer: Benjamin Thompson

The symptoms of a Salmonella food poisoning infection can be very unpleasant, but, thankfully, in most cases they only last a few days. However, Salmonella Typhimurium is a tricky beast – some of the cells in an infection have the ability to go into a sort of reversible state of suspended animation within gut tissue, becoming what are known as ‘persister’ cells. And these cells are super hardy when in this persister state. For example, they become temporarily impervious to antibiotics that would otherwise kill them. This ability makes treating an infection pretty tricky.

Interviewee: Wolf Hardt

So, you cannot use antibiotics for Salmonella diarrhoea therapy, and the reason is you will be able to clear the fast-growing Salmonella cells from the gut lumen, but as soon as you stop the antibiotic treatment, some Salmonella from somewhere – we assume from the gut tissue – will reseed your gut lumen and you are just as sick as before.

Interviewer: Benjamin Thompson

Wolf and his colleagues have been looking at Salmonella’s talent for temporary invulnerability, and they’re particularly interested in whether these cells could also be a reservoir of genetic resistance. They wanted to know whether persister cells could pass on antibiotic resistance genes to other bacteria in the gut, and they’ve got a research paper about it in this week’s Nature. Now, bacteria are extraordinarily promiscuous, and regularly share genes among themselves. One of the ways they do this is by passing tiny circles of DNA called plasmids from a donor to a recipient. That’s one of the ways that antibiotic resistance genes can spread. To find out the role that reawakened persister cells play in this promiscuity, the research team infected mice with a strain of Salmonella Typhimurium that contained a plasmid with an antibiotic resistance gene. They infected the mice either orally or by injection and then treated them with a different antibiotic – not one that the Salmonella was resistant too. This then killed off any free-living Salmonella, leaving just the persister cells hiding out in intestines of the mice.

Interviewee: Wolf Hardt

Then we were entering into a second phase of this experiment. We were asking what happens if we are now adding a second bacteria strain that doesn’t carry the plasmid yet into the mouse gut, so we could orally infect mice with a second wave of bacteria and then we could ask can we see at all that the resistance plasmids would end up in the population of the bacteria from the second wave, and the quick answer is yes, it did.

Interviewer: Benjamin Thompson

For this second wave, the team introduced both a strain of Salmonella lacking the resistance plasmid and a strain of E. coli, which is a common gut bacteria. They found that the resistance plasmid, hidden safely away in the persister cells, was able to spread to both sets of newcomers. And this happened quickly. In fact, only a small number of reawakened persisters and a couple of days were needed before 99% of the new bacteria carried the plasmid. What’s more, this transfer happened without any selective pressure. Normally, bacteria only keep hold of a plasmid giving resistance to antibiotic X, say, if antibiotic X is present. In this case though, the Salmonella persisters were never exposed to antibiotic X, and yet they kept hold of the plasmid and were able to pass it on. Wolf thinks that this system is an important one to consider when thinking about how antibiotic resistance can spread.

Interviewee: Wolf Hardt

So far, the general feeling is that the overuse of antibiotics is the key driver of this spread, and this is certainly true because as soon as you apply an antibiotic to animals or to infected people, you will select and help the resistance plasmid-carrying bacteria to bloom up, but we would like to point out that there are other mechanisms that will also help to spread resistance plasmids, and in our case, no use of antibiotics is actually involved.

Interviewer: Benjamin Thompson

Nathalie Balaban from the Hebrew University of Jerusalem also looks at antibiotic resistance in persister cells, but wasn’t involved in this research. She was impressed with the way it was carried out.

Interviewee: Nathalie Balaban

They really did very extensive work with different systems, doing it in vivo because experiments on persisters are often done in vitro where it’s much easier. Being able both to study this in a different model and then also to directly visualise persisters from the gut tissue itself is really a tour de force.

Interviewer: Benjamin Thompson

Of course, it’s important to note that this work was done in mice, so we’ll have to wait and see whether this method of spreading antibiotic resistance is of importance in other animals or humans. But if it is, what’s to be done to prevent this pool of persistent cells spreading antibiotic genes in the environment? Wolf’s got an idea.

Interviewee: Wolf Hardt

Well, the most efficient way to solve this problem is to prevent the infection, and we found out that you can actually reduce the formation of these persister cell reservoirs in the host tissue if you vaccinate the host before you infect with these plasmid-carrying Salmonella.

Interviewer: Benjamin Thompson

Wolf suggests that a vaccination strategy could be of particular relevance in an agricultural setting, where animals can be infected by multiple strains of Salmonella. Preventing the spread of antibiotic resistance is something that’s been highlighted by governments as being of worldwide importance, but achieving this will require a greater understanding of the underlying mechanisms, as Nathalie explains.

Interviewee: Nathalie Balaban

I think that new ideas come from these basic research directions and persisters is one example of a phenomenon that was seen in labs that can explain the failure of antibiotic treatment, so it is a fascinating example of a very basic science idea that slowly gains attention in the medical world that may lead to understand how to get rid of resistant bacteria by a different mode.

Host: Benjamin Thompson

That was Natalie Balaban from the Hebrew University of Jerusalem in Israel. You also heard from Wolf Hardt from ETH Zurich in Switzerland. You can read his paper over at nature.com.

Host: Nick Howe

At the end of the show, we’ll of course have the News Chat, where we’ll be hearing about a mysterious radiation spike. Now though, it’s time for the Research Highlights, read this week by Anna Nagle.

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Anna Nagle

You’d think that night-time predators would be darker in colour to remain hidden from their prey but for barn owls, bright plumage may actually help them hunt. An international team of researchers has found that whiter barn owls had better hunting success during a full moon. To find out why, they took taxidermied barn owls of different shades and zip-lined them towards voles under simulated moonlight. They found that under conditions like a bright full moon, the lighter owls were more likely to cause the rodents to freeze, making them easier to catch. The authors suggest that this may help explain why there is such a variety of colours in barn owls. Whilst lighter owls have better hunting success during a full moon, darker owls rule the roost on gloomier nights. Swoop on that research over at Nature Ecology and Evolution.

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Anna Nagle

Dogs – man’s best friend. But they haven’t always been this way, and in fact, it appears that humans have slowly moulded their brains over the centuries. A team of scientists in the US compared brain images of 33 dog breeds that differed in size and behaviour. They found clear differences in brain structure between breeds that weren’t just because of body size or head shape. In fact, these differences were linked with behaviours like guarding and companionship, and appear to be a recent feature of dog evolution. These findings suggest that humans have shaped the brains of our canine companions through selective breeding, and this could give insights into the link between their brain structure and behaviour. Go fetch that research over at the Journal of Neuroscience.

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Interviewer: Nick Howe

Since moving to London, I’ve found that it has a couple of problems. It’s busy and it’s noisy for a start, but one thing I didn’t expect was the heat. A few of weeks ago, Europe was in the midst of a heatwave and here in London, there were temperatures recorded as high as 36 ˚C – that’s around 97˚ F for our US listeners. Now, I can’t lay the blame for this entirely at London’s feet – it was hot all over the UK, but in cities it was particularly sizzling.

Interviewee: Gabriele Manoli

So, as a general trend, cities are warmer than the surrounding.

Interviewer: Nick Howe

This is Gabriele Manoli, a climate researcher at University College London. He’s describing what’s known as the urban heat island effect. Now, there are a number of reasons for cities to be hotter than their surroundings. For example, they’re filled with buildings using energy and emitting heat. There’s also buses, trucks and cars rushing around, which again warms things up. The effects of this go beyond being merely uncomfortable. In 2003, thousands of people in France died in a heatwave, many of them concentrated in cities like Paris. And hot cities are set to become more of a problem as the climate warms. Gabriele has been trying to better understand what causes urban heat islands, and in this week’s Nature, he’s got a paper out all about it.

Interviewee: Gabriele Manoli

We wanted to see if there are some global trends in terms of urban heat islands.

Interviewer: Nick Howe

To do this, Gabriele constructed a mathematical model using over 30,000 data points on city temperatures. By combining this model with data on different factors, like the size or complexity of a city, he was able to find what were the main things associated with the magnitude of urban heat islands.

Interviewee: Gabriele Manoli

And we were able to link the intensity of urban heat islands to only two variables –population and mean annual precipitation in the region.

Interviewer: Nick Howe

Now, it was already known that rainfall and population have effects on urban heat islands. A bigger population generally means the city is larger and denser, exacerbating any drivers of urban heating. But Gabriele was able to show that this is consistent across the globe. In terms of rainfall, it has been predicted that more rain in an area should lead to relatively hotter heat islands, which seems a little counterintuitive. To understand this, it’s important to know that urban heat islands are measured in comparison to their surroundings. So, in a place with high rainfall there are often lots of plants, and plants tend to cool down the environment as water evaporates from their leaves. So, rainy places tend to have lots of cooling plants everywhere, except in cities. That means comparatively the cities in these areas are much hotter than their surroundings. Gabriele again showed that this was the case globally, but only up to a point. Plants can only do so much, so at a certain level of rainfall the effect tails off. Because of this, Gabriele suggests that having more plants may help prevent urban heat islands in places like London, but for very rainy cities, like Singapore, it might not be so effective.

Interviewee: Gabriele Manoli

If you’re in a very wet place, let’s say the tropics, you need much more vegetation to reduce the temperature of the cityscape than if you are in a dry place, and this means that basically almost the entire city area should be vegetated if you want to reduce this warming.

Interviewer: Nick Howe

There’s not a one-size-fits-all to combat urban heating and so for tropical wet regions, different tactics need to be employed. So, what could be done to make life more bearable for city dwellers? I spoke to Jeffrey Raven, an urban designer who has been researching different design solutions to tackle urban heat islands. He has some ideas to help cool wet tropical cities.

Interviewee: Jeffrey Raven

The evidence that we have drawn from our research and actually testing it in different case studies is that the flow of air is actually quite important in tropical environments.

Interviewer: Nick Howe

Air flow can help lift warmer air out of the city and cool it. This could be accomplished by building cities to take advantage of the prevailing winds. For example, rather than blocking winds with buildings, parks can be placed that allow the cool breeze to flow through the city. Jeffrey also thinks that city-scale, land-surface temperature analyses like Gabriele’s are very useful, but we need more zoomed-in information.

Interviewee: Jeffrey Raven

Land surface temperature analysis that is at a much higher level needs to be then augmented by a more granular analysis that takes the form of actually getting into the actual urban centre itself, speaking to the local population and doing some basic analysis of climactic considerations in the microclimate of an urban district. This is important because we can then start to evaluate where are the priority areas in an urban district.

Interviewer: Nick Howe

So, rather than just looking at whole cities and trying to think of ways to cool them, Jeffrey suggests that identifying hotspots within the city and targeting them can make a bigger difference to urban dwellers. Preventing urban areas having such high temperatures is only going to grow in importance. Not only is climate change making temperatures go up, but more of us are moving to cities. Here’s Gabriele.

Interviewee: Gabriele Manoli

More than 50% of people now live in cities and these percentages are predicted to increase to something like 68% by 2050. So, definitely, this will affect a large portion of the population in the near future.

Interviewer: Nick Howe

That was Gabriele Manoli of University College London, previously at ETH Zurich where he did this work. You also heard from Jeffrey Raven, of Raven Architecture and Urban Design and the New York Institute of Technology. If you want to give Gabriele’s paper a read, then it’s over in the usual place.

Interviewer: Benjamin Thompson

Finally then on the show, it’s time, of course, for the News Chat and joining me once again is Lizzie Gibney, senior reporter here at Nature. Lizzie, thanks for dropping by.

Interviewee: Lizzie Gibney

Thanks for having me, Ben.

Interviewer: Benjamin Thompson

Well, our first story today is one that you’ve been looking into for Nature News and it centres on a tragic nuclear incident in Russia that happened a couple of weeks back, and this is a mystery that a lot of folks are trying to get to the bottom of.

Interviewee: Lizzie Gibney

Exactly, it is a bit of a mystery. So, information has been quite slow to emerge from official sources in Russia and there’s some speculation that it involved some weapons testing, and there’s also been lots of conflicting reports, so what we’ve tried to do is piece together exactly what we definitely do know, and then figure out how scientists are trying to understand what, from that, we can tell is likely to have happened.

Interviewer: Benjamin Thompson

Before we get into sort of the key questions then, let’s give a bit of background to what actually happened. There was an explosion of sorts in a Russian naval base.

Interviewee: Lizzie Gibney

That’s right. So, we know that there was an explosion. We know that very sadly, five people died, five scientists died and one of them used to work on one of the projects at CERN at the ALICE collaboration, and we know that it happened on an offshore platform and that at the same time, there was a big spike in gamma radiation that was seen at a detector about 30 or 40 kilometres away. But we didn’t, for a long time, know what kind of isotopes or kind of radioactivity was actually released, and then last week were told exactly what isotopes they were. So, that is a lot more helpful for scientists in terms of actually piecing together what might have happened, what might have exploded.

Interviewer: Benjamin Thompson

Yes, I imagine that an explosion will give away a bit of a fingerprint, based on the isotopes that are released. Is that the case?

Interviewee: Lizzie Gibney

Exactly, and what we know from these isotopes, so strontium-91, barium-139, barium-140 and lanthanum-140, they would all have been produced inside the core of a nuclear reactor, so the kind of nuclear reactor that would be producing nuclear energy, but likely much, much smaller. If it was critical, so the chain reaction was underway and it had exploded, these are the kind of isotopes that we would expect to see. But we would also expect to see some other isotopes if that had happened, so that’s a bit of a mystery. Is it that we just haven’t detected those? Is it that they have been detected but the authorities in Russia are not telling us that? Or perhaps they weren’t there, in which case maybe it wasn’t actually a reactor core itself that exploded but maybe it was some of their housing, some of the safety accoutrement that had some damage to it, which meant that some radioactive gases released but not actually the core itself.

Interviewer: Benjamin Thompson

I mean pretty nasty either way. What was the official line from the Russian government about this?

Interviewee: Lizzie Gibney

The official line is that there is no risk to public safety, which actually is something that most scientists also agree with from what we know, and they’ve said that there was some testing underway of a device that involved a liquid propulsion engine, but also these radioactive isotopes.

Interviewer: Benjamin Thompson

Well, there are suggestions maybe, Lizzie, that this was part of some sort of rocketry system.

Interviewee: Lizzie Gibney

Exactly, so this is partly based on where the incident actually happened. So, it was at a naval base and some scientists have been looking at satellite images that were taken in literally the hours before and after this incident happened, and they can see that there is some launch infrastructure there, so potentially for testing a missile, and also that there was a boat out in the bay that is often used to recover some kind of nuclear debris that might be radioactive. So, putting those things together, there’s been some speculation that this was actually a test of a missile that’s known in the west as Skyfall, a missile that could essentially just keep flying almost indefinitely because although it would use conventional means to get up into the sky, from then on it could be nuclear-powered which would mean it could just keep on going for at least days.

Interviewer: Benjamin Thompson

And you yourself have been speaking to the researchers trying to get to the bottom of what might have been going on. What sort of things are they trying to do?

Interviewee: Lizzie Gibney

There’s one scientist who’s trying to do a bit of citizen science really, trying to gather air filters out of people’s cars from the local area and get them to send them to him in the States. If he can analyse those quickly enough and compare them to this catalogue that he’s got taken from lots of different nuclear sites from across the world, that might help reveal what was going on at that particular site. There are some other teams who are using a completely different technique and trying to see what the scientists who sadly died in this incident, what they were working on, what kind of papers they published, who they collaborated with, and by doing that piece together what kind of activities they might have been doing.

Interviewer: Benjamin Thompson

And important to note there, as you say, this was a tragic incident and several people lost their lives.

Interviewee: Lizzie Gibney

That’s right. These were very eminent scientists as well in Russia, and that’s one of the question marks that hangs over whether way they were testing this particular missile because if they were, it seems very unlikely that you’d put a substantial amount of shielding on a reactor core that was going to be flying in the sky. So, that would mean that the tests were happening without shielding and these were some of Russia’s best scientists in this area, so that’s either quite worrying or suggests that that’s not what was going on. But these are all the kinds of things that people are using to try and figure out exactly what happened here.

Interviewer: Benjamin Thompson

Well, lots of questions that remain to be answered then, Lizzie, and listeners, head over to nature.com/news for more information on the research that’s ongoing at the moment. For the time being though, let’s move on to our second story and it’s a space story and well, later this week, the latest lunar lander is due to touch down on the Moon.

Interviewee: Lizzie Gibney

That’s right. This is India’s mission, Chandrayaan-2, and it would make India the fourth nation in the world to successfully soft land a lander on the Moon, so there is a huge amount of excitement about this at the moment.

Interviewer: Benjamin Thompson

Let’s talk about this mission then. What’s it designed to do?

Interviewee: Lizzie GibneySo, this mission is also the first that would be headed for the south pole. So, the Chinese mission, Chang'e 4, went to near-ish the south pole, but this really would be headed right to the south pole, which is incredibly interesting, both scientifically and in terms of potential uses in the future because that’s where we think the ice is on the Moon. But we’ve not really been able to chart how much there is, where it is exactly and how accessible it might be, so this would be a really big first step if this mission can try and understand a lot more about the ice at the south pole.

Interviewer: Benjamin Thompson

And the Moon is of great interest to a lot of nations around the world then – China had a lander that succeeded; Israel had one that didn’t. It’s obviously a very tricky thing to do. What are researchers saying about this one?

Interviewee: Lizzie Gibney

Well, it is. I think sometimes we forget when NASA continually lands landers absolutely everywhere around the Solar System that it’s actually really, really tough still. So, this particular mission is going to bring the lander down to about 35 kilometres and then it will have these thrusters to fire to slow it down rapidly from about 6 kilometres a second to almost nothing, and it has an AI guided landing system that is relatively untried and that’s going to look for a spot that’s relatively free of boulders to land in. So, if it all goes well, it will be really impressive, but there are going to be a lot of people at mission control holding their breath.

Interviewer: Benjamin Thompson

And one of the things that mission will be investigating are a phenomenon known as ‘Moonquakes’. I do think the name maybe gives away what they are. But what can you tell me about them?

Interviewee: Lizzie Gibney

So, the Moon has become a little bit skinnier over the past several hundred million years. As it shrinks, the kind of brittle crust breaks and then you get these little Moonquakes, and learning about these Moonquakes and actually observing them is going to help us to understand more about the Moon’s core and it’s kind of size and composition. So, there are lots of different elements alongside this learning about water at the south pole that hopefully we should be able to get from this mission.

Interviewer: Benjamin Thompson

Finally then on this one, Lizzie, another ambitious attempt to learn more about our closest neighbour in the Solar System. When can we expect the results?

Interviewee: Lizzie Gibney

So, it’s all set to take place on 7 September, and we should hear from the Indian Space Research Organisation, who is running this mission, whether it’s succeeded in the early hours, Indian time.

Interviewer: Benjamin Thompson

Well, thank you for joining us, Lizzie. Listeners, head over to nature.com/news for more on those stories.

Host: Nick Howe

That’s it for the show this week until we return next week with more stories from the world of science. In the meantime, you can get in contact with us. Feel free to send us a tweet – we’re @NaturePodcast – or if you’re not a tweeter, then you can email us at podcast@nature.com. I’m Nick Howe.

Host: Benjamin Thompson

And I’m Benjamin Thompson. See you next time.