Vampire bacteria, "hangry" males, and ants using moonlight
This month, Chris Smith hears how blood-thirsty bacteria sniff out wounds to trigger infections, how ants navigate at night, how male and female brains respond differently to starvation, and inflammation linked to premature labour...
In this episode
00:32 - Bacterial vampirism
Bacterial vampirism
Arden Baylink, Washington State University
Microbes have a thirst for blood, and they can actively sniff it out and swim towards it; it’s a process that, as he explains to Chris Smith, Arden Baylink, from Washington State University, dubs “bacterial vampirism” and it might give us a clue as to why people with certain inflammatory diseases develop the bacterial infections that they do, and open up new avenues to treat them…
Arden - We know that bacteria that colonise the human gut are important both for our health and also there are lots of bacteria that infect our guts and cause disease. And we know a lot about how these bacteria behave when they're infecting a healthy person. But what we don't know as much about is what happens when, for lack of a better word, a sick person gets infected. Because those are the people that we really have to worry about with people who have compromised immune systems or chronic disorders they can be susceptible for much worse infections. How do bacterial pathogens behave in the intestines of people with with diseases?
Chris - Any sick people in particular that you are interested in?
Arden - Yeah, there's this population of people, it makes up about 1% of people, that have something called an inflammatory bowel disease. And the most common forms of these are Crohn's disease and ulcerative colitis. And in these diseases people have inflammation of their intestines that last decades. And also ulcerations, basically intestinal bleeding. Not only that, these individuals are also very susceptible to lethal bacterial infections.
Chris - And what do you suspect is driving that relationship? How do you think the bacteria are sensing that some thing's amiss and therefore that they have an opportunity afforded to them by the presence of that disease?
Arden - So that question is actually what brought us to perform this actual study. So bacteria, you know, a lot of people have have seen a video of bacteria swimming around. Bacteria actually don't swim around aimlessly. They have a built-in navigation system where it's effectively a sense of smell. So they smell chemicals in their environment and that's how they know where to find nutrients, how to avoid toxic conditions. And so we wondered if there might be something different about the intestinal environment within diseased patients that these bacteria are drawn to that could be mediating these bloodstream infections.
Chris - So what did you do kind of mimic what goes on in the diseased intestine to see if you could sort of flush out what it was that the bacteria are effectively sniffing out?
Arden - Yeah, exactly. And so in this case, because it was the first study looking at this question, we actually made a model in the lab at a microscopic level that simulated intestinal bleeding. We took a very small glass capillary and we injected human serum, the liquid part of blood. And then what we could do is we could couple that with a microscope and actually watch in real time to see how these bacterial pathogens responded to that source of human serum.
Chris - And is your hypothesis that if they are drawn to it like bees round a honeypot, I suppose that there must be something about what's in there, the chemical cocktail that's in that serum that pulls in the bugs?
Arden - Right! Yeah. And and that's actually what we saw within 10 seconds, the bacterial pathogens are actually swimming towards that site of human serum. And our thought was, well, there must be something in that blood serum that the bacteria like that is beneficial to them. That brought us to the next stage of the study, which was, you know, well what is that component, that part of human, human blood serum that these bacteria are seeking out? And through a lot of experiments that we did, we were able to hone in on this amino acid called serine. And serine is one of the most important foods that bacteria can encounter. And they actually have a specialised system to be able to detect serine in their environment. And so what we ended up finding was that this serine in your blood seems to be an attractant for these bacteria. And not only an attractant, but they use it as food.
Chris - And do you know how they taste it? How they're detecting it so they can respond in the way that you've identified?
Arden - Yeah, this navigation system that bacteria have that I mentioned earlier it's something called chemotaxis. And in chemotaxis there are these specialised protein receptors and each of these protein receptors can sense certain molecules in the environment. And it turns out that a lot of the bacteria that are involved in bloodstream infections that we were looking at actually have a specialised chemoreceptor protein that detects and binds the amino acid serine.
Chris - That's exciting. So the obvious question off the back of that then is if you knock out that effect or that receptor, can you block the effect and could we therefore exploit something like that medically to basically blind the bacteria to their food source?
Arden - That exactly is one of the long-term goals of this work. We think that this interaction seems to be very important for mediating the pathogens attraction towards blood serum. And we also think that there are some other receptors involved. And so, so maybe kind of the best version of this future drug could be a drug that actually blocks multiple receptors of this pathway. But certainly that that could be something that could be therapeutic for, for patients with inflammatory bowel diseases.
Chris - So in essence, these, these bacteria actually really vampires, aren't they? <Laugh> they're sort of homing in via these receptors. They've evolved to, to track down our blood and then feast off it.
Arden - That was our thought as well. You know, so we see that, that these pathogens are attracted to blood serum and they eat it. They use it as food. That's why we actually coined this new type of pathogenesis strategy called bacterial vampirism. And one thing that was really interesting about this work is that a few weeks after it was published actually I was contacted by a number of patients with cases where, after they had read the paper that we had published, they actually thought that they have experienced something like this. And so we're still sorting through that data and trying to make sense of it, but the insight into this new pathogenesis strategy might actually have some traction for some certain types of infections that these patients have been experiencing.
07:04 - Ants navigate by moonlight
Ants navigate by moonlight
Cody Freas, Macquarie University
Finding your way around is a critical survival skill, especially for social insects like ants, which forage away from their nests over long distances, but have to find their way home afterwards. Some ants do it by laying down chemical “breadcrumb” trails, while others count their steps in any direction and also rely on visual cues, making mental images of the landscape to guide them. But now, speaking with Chris Smith, Cody Freas, from Sydney’s Macquarie University, explains how he has uncovered another ant navigation tool, which works even at night: they can see the polarisation pattern of sun and moonlight, which gives them a directional reference to follow…
Cody - Most of what we work on is ants that are active during the day. And what you find is that there's also quite a number of species that due to things like predation or some desert ants species where it's way too hot during the day, such as in Phoenix, Arizona where it's 45 degrees will shift their activity into the night. And we wanted to know, well these ants are still really good at being able to get to goal locations, such as back to the nest with food. How do they do that when there's really no light levels or anything in the sky that should be able to guide them?
Chris - Ants use a range of different ways to navigate though, don't they? We, we've had papers charting how they use pheromones and lay down trails. Also, a few years back people realised they were counting their steps in some cases by extending the length of an ants leg, you could make it walk too far, for example. So it was obviously counting. So where does, does visual guidance fit in then?
Cody - A lot of ants don't use pheromone trails for a number of different reasons. The step counter forms part of what's called path integration. So you can count your steps, but if you don't know what direction you're going, that doesn't really give you very good information. And funny enough, that's what this sky compass is for. It's the directional component of that estimate. So if you're counting your steps going one way underneath the sky and then counting your steps going another way, that integrates into what we call a vector. But ultimately what that is is just an estimate of how far you've traveled and in what direction away from the nest.
Chris - And the key thing of course is you've gotta know the direction?
Cody - Yeah. So that's what the celestial compass or sky compass can give the ant while it's counting its steps.
Chris - You're calling this the sky compass. What does that involve? Is this stars? Is it moonlight?
Cody - So we don't know of ants using stars, but mostly it's the sun. So the sun or the moon creates a pattern across the sky through what we call polarised light. And polarised light occurs as light enters the atmosphere. It becomes linearised where it's only in one single direction. Think of it as just the light wave going up and down. And that creates a pattern across the sky that many different insects can see, which is very useful because then the insect doesn't actually need to see the sun or moon if they, let's say like the ants in this paper live in a forest so there's patches of sky where they can see the sky, but they can't always track where the sun or the moon are throughout the day or night.
Chris - And presumably also if it's cloudy which might obscure the disc of the sun or the moon itself, the polarised light is still gonna penetrate. So they're still gonna see that signature...
Cody - Yeah. So when the sun is obscured by canopy or when it's even below the horizon, that pattern is persistent. It changes as the sun or the moon moves, but it's still visible throughout the night, which is very useful and makes it a very stable cue for these ants in order to continually be able to navigate because they go out during twilight, so right after sunset. And they could stay out for 12 hours before they come in overnight.
Chris - So what convinced you that they are using this cue? How did you prove that it is the orientation of the polarisation of the light coming from the moon in this instance that is driving this?
Cody - What happens when the sun or the moon, when they get near the horizon, the polarised light pattern in the sky is kind of concentric circles. So think bigger, bigger circles out from the body itself. And so when it's below the horizon, you get this very clear and very strong polarisation pattern that's north and south. And thus you can take a linear polariser - so think of sunglasses that kind of make it to where, when the sun is in the top of the sky, there's not a whole lot of light passing through from the horizon - it's the same thing. When the sun is near the near the horizon, the top of the sky has the most polarised light. So what we can do is take a big 30 centimetre wide polar filter, place it over the ant and orient that in different ways. And what we hope to see and what we see is that the ant will update their heading based on the rotation that we create in the overhead pattern.
Chris - Got you. So you're saying you study ants that have left their nest and got a fix, a bearing, on the sky based on the polarisation pattern when they left the nest, you then fool them by rotating that light with a filter and if they are genuinely following that polarisation orientation, they'll go in the wrong direction. Is that what you saw?
Cody - Yeah. So we shifted 45 degrees either clockwise or counterclockwise. And what you end up getting is they'll shift their heading direction 45 degrees and then once they leave the polarised filter, they'll shift back and a metre later they'll be reoriented back to the right direction suggesting both they detect that change that's occurring in the overhead sky. And then when they see this, the real sky again, they shift back.
Chris - Moonlight though is very, very weak compared to sunlight during the day. How do their eyes manage to detect such a weak signal?
Cody - Their eyes are extremely sensitive to different types of light, polarised light in particular. Insect eyes have what's called dorsal rim area of the eye that's highly sensitive and it's on the top of the eye. It's just a region that's highly sensitive to both UV light and polarised light. And what you see in these ants is they have huge eyes for their head and thus they're much more sensitive to low light levels than we we would be.
Chris - Even when the moon is like a crescent compared to a full moon?
Cody - Yeah. So that was something that was a little bit unexpected. What we assumed is that there would be a clear minimal where the moon was no longer very useful, but even when there's 25% of the moon that is projecting this pattern, they're still able to detect it and use it in order to orient.
Chris - And what about when there's a new moon? In other words, there is no moon in the sky at night. It's visible in the day. What do they do then?
Cody - So then it's important to know that this isn't the only cue they're using. They're also really good at memorising images of the surrounding trees. So when there's no celestial compass, they've really gotta fall back on the visual cues of the, what we call the panorama. And they take these snapshots of views in different orientations and then they're able to compare a memory of the panorama on the route and their current one in order to orient.
Chris - Given that they're going to be inherently at greater danger at that time, because they've lost one of their main navigational devices - it's like me going for a drive without my GPS these days, I'm more likely to get lost! - do they compensate by fewer of them foraging or not foraging as far when they're in that phase of the moon?
Cody - Yeah. So you get a difference of about 25% more individuals go out on nights where the moon is visible versus on new moon nights, forgers still do leave and come home without the moon, but they're much slower as well. So clearly they're pausing and trying to collect light when there's no moon. And they're much faster coming home when there's a clear signal from the moon when it's near full.
15:11 - How brain metabolism responds to calorie restriction
How brain metabolism responds to calorie restriction
Nathalie Rochefort, University of Edinburgh
Men and women respond differently to severe calorie restriction. Men sacrifice fat to preserve muscle mass, while women do the opposite, surrendering muscle bulk to maintain their fat mass. So how does the brain respond, and does it too differ between the two sexes? That was the question that Edinburgh University’s Nathalie Rochefort set out to answer in mice, and she’s found that the answer is very intriguing. As she outlines to Chris Smith, male mice, as they shed fat, also drop their levels of a fat-signalling hormone called leptin, which in turns signals to the brain to enter an energy-saving state, which functionally de-tunes at least some elements of cognition. Females, on the other hand, which preserve their fat and hence leptin, don’t suffer the same fate…
Nathalie - It's known that in times of food scarcity, males and female bodies react differently in the peripheral tissues. So for example, females will tend to lose muscles and bone mass, while they tend to be more resilient in losing fat mass. It's also known that females are more likely to suppress energy costly reproductive functions to save energy. So these differences in peripheral tissues had been well-documented and we wanted to know whether the brain would contribute to these energy saving mechanisms.
Chris - Because the sort of dogma when it comes to the brain and the central nervous system is that we preserve that in terms of blood flow and everything else against all odds. So are you about to tell me that that is not the case then?
Nathalie - Well, the brain consumes a lot of energy. Despite the fact that it represents only 2% of our body mass, the brain consumes 20% of our calorie intake. What is known also is during evolution and in different species, the availability of food can defer very substantially between, for example, winter or spring or also just in times of food scarcity. And so we were interested in how the brain can adapt its function depending on the energy availability. An analogy is, for example, the phone. So when there is less power, it can go in the low power mode and it could still function, but maybe the phone would use less energy and would function maybe a bit less well.
Chris - How did you do this then?
Nathalie - So we use different techniques to image energy consumption in the brain using fluorescent markers to know whether there was a difference in energy consumption between male mice and female mice that were fed normally, and between male mice and female mice that were food restricted from two to three weeks. These mice that were food restricted lost 15% of their body weight. It's quite substantial. So this is an animal model of a long-term, quite drastic food restriction corresponding to this 15% body weight loss.
Chris - And when they're in that almost starving state, do you see the peripheral tissues, muscles and so on, responding accordingly as you would expect in both the males and the females Along the lines you were mentioning where there's relative preservation of the fat in the females, relative preservation of the males muscles?
Nathalie - Yes. What we tested directly was a hormone, the leptin hormone, that is secreted by fat mass. So when an animal is food restricted, lose fat mass, the level of leptin is decreasing. And what we saw consistent with the literature was that the females tend to keep their fat so they lose weight. But this weight loss is not due to the fat loss, but more due to muscle loss. And why is it important? Because in our previous publication we show that the leptin was a key hormone to tell the brain whether it should be in a high power mode or a low power mode. So if a male mouse is food restricted, lose weight, lose fat, decrease of leptin levels, then the brain enters a low power mode, the cells will use less energy and will function a bit less well. If you give leptin to the animal, the brain goes back to a high power mode. What happens in the females is that this hormone level, it stays high because the females keep their fat mass. So the females do not enter the low power mode.
Chris - What are the functional implications of that in terms of neurological function? Does this mean if you've got your visual system turning down its metabolism to spare energy consumption, that you are gonna be seeing less well? I mean I know the visual system's a bit less important in mice, but if this was man instead of mouse, is there a functional consequence of doing that for the males?
Nathalie - Yes. That's what we have shown. Not only the neurons start to enter this low power mode, so they use less energy, but also their function is affected. We tested that in two ways functionally by recording the activity of the neurons directly in the visual cortex. We used the visual cortex just as a model, 'cause it's easy to test. You can show a visual stimulus and test whether the animal can see or not. So when we did that, when we recorded the activity of these neurons, we could see that their response to different images, the coding precision of the neurons in the visual cortex was degraded in times of food restriction.
Chris - Do you think that the visual cortex is representative of what's going on in the brain in general? Because obviously the visual cortex, certainly in a visual species like us, has a huge blood supply and a huge metabolic demand. If you were to look at another bit of the brain, say, I dunno, the frontal cortex for example, would you see the same thing? Do you think this is gonna cause a global impairment of the male brain in starvation or is it gonna be limited and restricted to certain neurological domains and functions?
Nathalie - We do not think that this is specific to the visual cortex. We haven't tested other areas. It could well be that some areas are more protected, let's say, or prioritised during times of decreased energy availability. What we saw in females was that the energy consumption, the function of the neurons, the expression of different proteins were not affected during food restriction as much as in males.
Chris - Does this mean that males are more prone to get "hangry"?
Nathalie - <Laugh>? Well, maybe it does mean male and female bodies do react differently to food restriction and that the brain is not an exception. So there are many, many consequences or many impacts of this study. One is really that the cortex contribute to sex specific energy saving adaptations in response to food restriction. And that it should really be considered in studies manipulating the diet or assessing neural functions following different types of diets or restriction. It should really be tested both in males and females, keeping in mind that it's likely to induce different mechanisms.
22:60 - Predicting preterm labour risk
Predicting preterm labour risk
Nardhy Gomez-Lopez, Washington University
Babies born prematurely, in other words before 37 weeks’ gestation, are at increased risk from complications, which can include infections, neurodevelopmental problems, low birthweight and breathing difficulties. The impacts can be mitigated with suitable forward planning and interventions: for instance, sometimes preterm labour can be arrested to allow the baby to grow for longer, or to buy time for drugs that can mature the respiratory system to take effect. The issue though is knowing how is likely to be affected. All too often, women present already in the throes of labour, and an elective process becomes an emergency. Seeking to solve this with a screening test that can pick up women at risk is what has motivated Nardhy Gomez-Lopez, at Washington University. As she explains to Chris Smith, she’s found that pre-term labour seems to be linked to a heightened inflammatory state in the genital tract. This might be one way to solve the problem…
Nardhy - How can we identify a woman who eventually will deliver preterm is because she presents with symptoms of labour and that may be too late. And those women end delivering preterm in several days after they have this episode of labour. So what we wanted to do is measure a marker in the vagina during every pregnancy that will allow us to identify these women and what type of preterm baby, because there are many different types of preterm birth.
Chris - What fraction of pregnancies have this problem of preterm labour?
Nardhy - In Michigan where we conducted the study, the rate of preterm birth could be up to 15%. Nationally, one of every 10 babies is born premature in the United States.
Chris - And what do we do at the moment to spot people who might be at risk? Do we take, for instance, a past history of this happening to someone as a risk factor? Are, are there ways when we can sort of profile people or are we not very good at picking this up?
Nardhy - Well, right now we have limited strategies. One of them is the history. That's a factor that will increase the chances of this woman to have another preterm baby. The other one is measure the cervix. Utilising an ultrasound system, a short cervix, which is defined as less than 25 millimetres, is a risk factor for delivering preterm. And so far the only strategy to prevent prematurity is administration of natural progesterone vaginally to those women who had a short cervix. But this is a very small population of women. Therefore the preterm deliveries cannot be predicted or prevented.
Chris - And obviously having to go through those sorts of interventions and monitoring that's invasive. It's not ideal. It's also quite labour-intensive, isn't it? So you are searching for a better way to do this with minimally invasive techniques. How are you trying to do it? Yes.
Nardhy - Yes. So what we were trying to do is to find marker that measuring this marker, we can identify women who are at risk of delivering preterm earlier in gestation before any symptoms. So what we did is to recruit women and then we sample them throughout gestation. We have approximately 500 women who deliver at term and 250 that deliver preterm. How do we sample these women? We have vaginal swabs. And then we did simple assays to identify specific immunological mediators implicated in the disease.
Chris - So the, the thrust of this is you are looking to see when we swab these women, are we finding signs that there is a difference in how the immune system is performing in some of them and specifically those that are destined to have a preterm labour compared to the ones that don't?
Nardhy - Exactly. We found that those women who are destined to have a premature baby have inflammatory signal from very early in pregnancy. And that utilising these signatures, we can identify those women who eventually will have preterm baby.
Chris - If you were to use this then as a screening tool in order to try to predict a person who is at risk of this happening to her, what's the sensitivity and specificity based on these immune markers that that will happen to a woman?
Nardhy - The specificity and sensitivity were not directly addressed because this is a proof of concept study. But we did specific modeling to tell you confidently that these inflammatory signals can allow us to predict with a good predictive value, a subset of these women who eventually will deliver preterm. We cannot predict all preterm birth with this marker, but we can identify a subset of women who will eventually deliver preterm before 34 weeks gestation.
Chris - One of the criteria to do a screening programme is that we need to be able to do something about the thing we are screening for. So knowing that this may happen to a woman, does that mean you can intervene meaningfully because you've got advanced warning and stop that preterm labour happening?
Nardhy - Exactly. That's the point. To identify those women who will benefit from treatments. So right now we don't have a specific treatments for different types of preterm birth. So the idea is to identify a specific subset of women that eventually will deliver preterm and then perform more research to identify therapies for those specific subset of women.
Chris - And do you know why these groups of women who are going to have preterm labours have this more inflammatory state in the vagina? Do you know what's provoking that?
Nardhy - The short answer is we don't know. It is taught that the vaginal microbiome or changes in the bacteria that live in the vagina may allow us to identify women who eventually deliver preterm. And what we are doing right now is to integrate these inflammatory signals with specific microorganisms to see whether the combination of these two can help us to identify more women than the inflammatory signals alone.
Comments
Add a comment