Scientists pinpoint when harmless bacteria became flesh-eating monsters

Bacterial diseases cause millions of deaths every year. Most of these bacteria were benign at some point in their evolutionary past, and we don’t always understand what turned them into disease-causing pathogens. In a new study, researchers have tracked down when this switch happened in a flesh-eating bacteria. They think the knowledge might help predict future epidemics.

The flesh-eating culprit in question is called GAS, or Group A β-hemolytic streptococcus, a highly infective bacteria. Apart from causing flesh-eating disease, GAS is also responsible for a range of less harmful infections. It affects more than 600m people every year, and causes an estimated 500,000 deaths.

These bacteria appeared to have affected humans since the 1980s. Scientists think that GAS must have evolved from a less harmful streptococcus strain. The new study, published in the Proceedings of the National Academy of Sciences, reconstructs that evolutionary history.

James Musser of the Methodist Hospital Research Institute and lead researcher of the study said, “This is the first time we have been able to pull back the curtain to reveal the mysterious processes that gives rise to a virulent pathogen.”

Genetic gymnastics

Musser’s work required analysis of the bacterial genetic data from across the world – a total of about 3,600 streptococcus strains were collected and their genomes recorded. It revealed that a series of distinct genetic events turned this bacteria rogue.

First, foreign DNA moved into the original harmless streptococcus by horizontal gene transfer – a phenomenon that is common among bacteria. Such DNA is often provided by bacteriophages, viruses that specifically target bacteria. Picking up foreign genes can be useful because it can improve the bacteria’s survival.

In this case, the foreign DNA that was incorporated in the host’s genome allowed the streptococcus cell to produce two harmful toxins. A further mutation to one of these toxin genes made it even more virulent.

According to Musser, another horizontal gene transfer event made a good disease-causing pathogen into a very good one. The additional set of genes allowed it to produce proteins that suppress the immune system of those infected, making the infection worse.

Marco Oggioni of the University of Leicester said, “Because this study used data of the entire genome, all the genetic change could be observed. This makes it possible to identify molecular events responsible for virulence, as you get the full picture.”

Musser could also accurately date the genetic changes in GAS by using statistical models to, as it were, turn back the clock on evolution. They say the last genetic change, which made GAS a highly virulent bacteria, must have occurred in 1983.

Continental drift

That timing makes a lot of sense. “The date we deduced coincided with numerous mentions of streptococcus epidemics in the literature,” Musser said. Since 1983, there have been several outbreaks of streptococcus infections across the world. For example, in the UK, streptococcus infections increased in number and severity between 1983 and 1985.

It is the same story for many other countries, with Sweden, Norway, Canada and Australia falling victim to what is now an inter-continental epidemic. The symptoms ranged from pharyngitis to the flesh-eating disease, necrotizing fasciitis.

“In the short term, this discovery will help us determine the pattern of genetic change within a bacteria, and may help us work out how often bacterial vaccines need to be updated,” Musser said. “In the long term, this technique may have an important predictive application – we may be able to nip epidemics in the bud before they even start.”

What Musser is suggesting is that if enough bacterial genomes are regularly recorded and monitored, there is a chance that mutations or gene transfers, such as those GAS experienced, could be found ahead of time.

But Oggioni is sceptical. “While making such predictions may not be possible, this research will have other applications,” he said. “Knowing which genetic changes happen when can help tailor drug discovery research in a certain direction.”

Oggioni added that Musser’s work with GAS is only a model. Using Musser’s methods to record the evolutionary histories of other pathogens could be quite useful to tackle the diseases they cause now and, perhaps, even those that they may cause in the future.The Conversation

Written with Declan Perry. First published on The Conversation. Image credit: Zappys Technology

The only reason zebras have stripes is to ward off flies

Zebras’ stripes have baffled biologists since Charles Darwin. Many hypotheses have been proposed regarding their purpose but, despite hundreds of years of study, there remains disagreement.

In an attempt to end the debate, researchers have pitted various models against each other and systematically analysed data from past studies. Their results reveal the one reason zebras have stripes: to ward off flies.

A handful of ideas regarding zebras’ stripes have found some support among biologists. One proposed that the dark and light bands change how air flows around a zebra’s body and helps in heat management, which could go a long way in the hot tropical areas that zebras live in.

Another proposed the stripes were used by zebras as a way of social interaction. They may use them to identify other zebras and for bonding as a group in the wild.

A third proposal suggested zebras used the stripes as camouflage. While stripes are clearly visible in the day, there some thought that it helped at dawn, dusk, and in the night.

All these ideas were shot down when tested rigorously. Two others, however, remained intriguing.

Now, how do I get rid of these ants?
dkeats, CC BY

The first was that the stripes were used to dodge predators. It is called the “motion dazzle hypothesis”, and it suggests predators are confused by zebras’ stripes and cannot understand their movement. Research published in the journal Zoology in 2013 used a simulated visual system to show that zebra stripes do interfere with visual perception. But this is a difficult hypothesis to test in the field.

Martin Stevens at the University of Exeter has researched the motion dazzle hypothesis by getting human subjects to catch moving stripy objects on a computer. “It’s an artificial experimental system,” he admitted.

The second proposal was that stripes helped keep flies at bay. Zebras are especially susceptible to biting flies due to their geographic spread. These flies, which include the tsetse fly, stomoxys stable flies, and tabanid biting flies, are particularly prevalent in areas with high temperature and humidity – exactly the areas where zebras are normally found.

Bites from these flies can be nasty and, quite literally, draining. About thirty flies feeding for six hours on just one horse can draw as much as 100mL of blood. Usually the flies can number in the hundreds around one animal.

Zebras have shorter hair than other equids – the family that includes horses, donkeys and zebras – which may also increase their susceptibility to attack. Also, four diseases which are fatal to equids have been found in Africa. This could mean that investing in anti-biting defenses such as stripes is especially important for zebras compared to non-African equids.

It is possible that the dazzle effect acts on flies, rather than larger predators, and deter them from biting. “Stripes clearly have a number of functions,” Stevens said, “and these could be interacting in zebras.”

Revealing maps

In the new research, just published in Nature Communications, Tim Caro and his colleagues at the University of California in Davis, didn’t perform experiments. Instead they used ecological and observational data on zebras’ geographical locations and related factors. It is the first time that a comparative approach has been applied to find the reasons for zebras’ characteristic colouration. Caro thinks his findings may have nailed the answer at last.

Caro looked at seven species of equids and scored them for number and intensity of stripes. Just to be sure, they tested all five hypotheses regarding zebra stripes’ use: camouflage, predator avoidance, heat management, social interaction, and warding off flies. The extent of overlap between the geographic distribution of striped equids with each of these five measures was calculated.

E. greyvi, E. burchelli and E. zebra have stripes on all their bodies. Other equids don’t.
Caro, Izzo, Reiner, Walker and Stankowich

“The results were a shock to me,” said Caro. Of these five proposals, only warding off flies had statistical support. He had not expected such a clear-cut answer to the question. As the map shows, the only places where flies and equids live together are areas that are populated by striped equids.

The exact mechanism by which stripes deter flies remains unknown, but experimental studies performed by researchers at Lund University in 2012 have found support for this proposal. They created striped surfaces and stuck glue on them. Based on the number of flies on the surfaces with different thicknesses of stripes, they concluded that these flies stayed away from stripes as thin as those found on zebras.

“As is normal in science you get a solution that asks more questions,” Caro said. It is time to hand the problem over to vector biologists, who can understand the susceptibility of horses to biting flies.

In Darwin’s days, people didn’t consider animal colouration with respect to fitness advantages. “People thought that animal colouration existed simply to please humans or was caused directly by the environment,” Caro said.

Darwin “would be delighted” that researchers are now considering animal colouration as a functional trait, he said. We might not have all the answers regarding zebra stripes – but it seems we may be looking through the right lens.The Conversation

Written with Angela White. This article was originally published on The Conversation. Header picture credit: eoghann, CC-BY-NC.

Why one hectare of tropical forest grows more tree species than the US and Canada combined

One hectare of land in a tropical forest can hold 650 tree species – more than in all of Canada and the continental US. This has left biologists baffled for decades. Now, with advances in data analysis, Phyllis Coley and Thomas Kursar of the University of Utah may have finally found an explanation.

From a broad perspective, evolution is pretty simple. Successful species survive and reproduce, which depends on how readily they obtain resources. So if two species are too similar in their use of resources, they would compete with each other – unless one evolves to use a different resource and exploits a niche that hasn’t been filled. However, in any environment, niches are limited. That is why the diversity in a tropical forest cannot be explained by the exploitation of niches alone.

The competition for niches is shaped by species’ interactions with the environment, which includes both abiotic elements (climate, water, soil and such) and biotic elements (in other words, other species). Tropical forests have stable abiotic environments, so Coley and Kursar concluded it must be the biotic interactions that explain the extraordinary diversity in these forests.

They argue, in an article just published in Science, that an arms race between plants and plant-eaters is what drives evolutionary changes. When a plant-eater finds a new way to attack a plant, the plant must evolve to fight the plant-eater. Through many generations these changes force formation of new species, leading to the observed tropical diversity.

This explanation is known as the Red Queen hypothesis, which gets its name from a statement the Red Queen made to Alice in Lewis Carroll’s “Through the Looking-Glass”:

Now, here, you see, it takes all the running you can do, to keep in the same place.

The Red Queen Hypothesis is not new. It was first suggested in 1973, and has been applied to many other ecological scenarios. However, so far, biologists have found it hard to determine whether it applies to tropical forests because of the sheer size of the task. Tropical forests have thousands of plant species that may have hundreds of plant-eaters each. These millions of interactions need to be all taken into account to show the Red Queen hypothesis at work.

Also, in such an arms race, plants have it harder than herbivores, because their lifespan can be hundreds of times longer than the average leaf-eater, which is usually a small insect. That is why a single tropical tree may have hundreds of distinct chemical compounds in its defence arsenal against herbivores, which makes the analysis harder.

This is where advances in data analysis prove handy. To understand these defences on an ecosystem scale requires the use of metabolomics, which is the study of chemical fingerprints left behind by an organism.

Metabolomic analyses across forests in Mexico, the Amazon and Panama, show that neighbouring plants mostly have different defences than would be expected if it were a random process – in other words the Red Queen seems to be in action. Most convincingly, closely related trees and shrubs have often diverged defences, which is a sign of exploring biotic interaction niches, but have similar non-defence traits, which results from similar abiotic conditions that they find themselves in.

Coley said that, while the data seems convincing, there are still limitations. Tropical forests have been studied well, but there is no comparable data from the temperate regions, which would be needed as a control to validate the hypothesis. Perhaps such an arms race also occurs in temperate regions that have been studied less. Also, temperate regions are purported to have less diversity in tree species, but that may not actually be true, according to Jeff Ollerton, professor of Biodiversity at the University of Northampton.

In a 2011 study published in the journal Functional Ecology, Angela Moles, the head of the Big Ecology Lab at the University of New South Wales, looked at all the data on interactions between plants and plant-eaters. She found only a third of the studies showed there to be more interactions among tropical species than those at higher latitudes, such as temperate regions. But this meta-analysis (a method to meaningfully compare different datasets) showed that the positive results are not statistically significant. Worse still, only nine out of 56 comparisons showed that chemical defences were higher in tropical plants than in temperate ones.

Also, some recent work has called out biologists for depending on the Red Queen hypothesis for many explanations. A small but vocal group of researchers argue that other processes can explain diversity. Chief among the alternate explanations is the idea of genetic drift, where some genetic mutations are passed on to progeny randomly. This differs from natural selection, where nature actively chooses which mutations get passed on.

While Coley remains confident that the Red Queen hypothesis will indeed prove to be a satisfactory explanation, she also knows that a lot more data will be needed to get there. Previously, the limitation was data analysis; now it is data collection. Researchers have no option but to go out in a tropical forest, search for plants and their herbivores, and then record their interactions.

While other explanations will certainly have some role to play, Coley and Kursar make a persuasive case for why nature seems to have endowed tropical regions with so many plant and plant-eating species. Although Alice may not like it, we may have to thank the Red Queen for it.The Conversation

First published at The Conversation.