Traces of a bacterium related to syphilis have been found in a bone from a person who lived in the mountains of Colombia over 5000 years ago.

The discovery shows that this group of corkscrew-shaped bacteria was infecting humans thousands of years earlier than previously thought, before the rise of intensive agriculture, which many researchers consider a catalyst for the spread of pathogens.

Today, three subspecies of the bacterium Treponema pallidum cause the diseases syphilis, bejel and yaws. The deep history of these ailments is murky, and researchers have debated where diseases like syphilis arose and how they became widespread. Ancient bacterial DNA and markers of infection on skeletal remains lend us some clues, but these are rare and can be ambiguous.

So, when researchers studying the ancient DNA of 5500-year-old human remains in the Bogotá savannah detected the genome of Treponema pallidum in a human leg bone sample, it was a surprise.

“This finding was completely unexpected, because the individual studied had no skeletal evidence of a Treponema infection,” says at the University of California, Santa Cruz.

It is widely thought that many common diseases started to affect humanity after the dawn of intensive agriculture, when people began living in denser communities. But this individual lived in a very different context, where small hunter-gatherer groups travelled frequently and were in close contact with wildlife.

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“Our results can tell us a lot about the long-term evolutionary history of [this bacterium] by revealing a long-standing association with human populations,” says at the University of Lausanne in Switzerland.

When Broomandkhoshbacht, Bozzi and their colleagues compared the ancient genome to those of other T. pallidum bacteria, they found it was part of a completely different lineage from any known modern relatives. This indicates that, millennia ago, ancient relatives of syphilis had already diversified in the Americas and were infecting humans, and the team’s analysis suggests they had many of the same genetic features that make today’s strains harmful.

The findings point to an early presence of these pathogens in the Americas, but it is also possible that they have been infecting humans for even longer across the world.

at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, notes that the ancient strain might belong to an elusive, “missing” pathogen: Treponema carateum, which causes a skin disease called pinta. The bacterium is only known from physical descriptions, not genetics.

at the University of Zurich, Switzerland, wonders what additional ancient genomes can tell us. “Were there perhaps many extinct lineages and perhaps different diseases caused by these pathogens in the past?” she says.

For Bozzi, understanding how pathogens evolve to cause diseases like syphilis and yaws is a crucial step in finding the genetic quirks that allow pathogens to infect new hosts and make their associated illnesses more dangerous.

A toxin produced by bacteria found in dirty water kills off immune cells in the lining of the colon, meaning people whose guts are colonised by these bacteria are much more likely to develop a condition known as ulcerative colitis.

That is the conclusion of a series of studies in people and animals conducted by at Nanjing University in China and her colleagues. If this finding is confirmed, it could lead to new treatments for the condition.

Ulcerative colitis is one of the two main kinds of inflammatory bowel disease, or IBD. It is characterised by inflammation of the lining of the colon and rectum. People typically have periods of no symptoms that alternate with flare-ups. The most serious cases can require the removal of the colon.

The causes of ulcerative colitis have been uncertain, but it is usually regarded as an autoimmune disease with complex environmental and genetic causes. Zhang and her team suspected that immune cells known as macrophages might play a role.

Macrophages are found in most tissues in the body, where they mop up any debris or bacteria and also help regulate local immune responses. They can sound the alarm to call in more immune cells, causing inflammation, but – crucially – they can also sound the all-clear, reducing inflammation.

In colon tissue taken from people with ulcerative colitis, the researchers found lower levels of resident macrophage cells than in people without the condition. They then showed that killing macrophages in the colons of mice made them more susceptible to colitis. The researchers think the loss of the protection usually provided by the macrophages results in the lining of the colon becoming damaged and inflamed.

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But why were macrophage levels lower in people with ulcerative colitis? By testing samples of faecal bacteria from people with the condition, the team found a toxin called aerolysin, which turns out to be highly damaging to macrophages but has little effect on other cells in the gut.

Aerolysin is produced by some strains of bacteria in the genus Aeromonas, which are commonly found in fresh and brackish waters. The researchers call the strains that produce aerolysin MTB (macrophage-toxic bacteria).

When the team deliberately infected mice with MTB, this made them more susceptible to colitis. But if the gene for aerolysin was deleted from the bacteria, or if the toxin was neutralised by antibodies, the mice didn’t become more susceptible to colitis.

Finally, the researchers looked for Aeromonas bacteria in stool samples. They found them in 72 per cent of 79 people with ulcerative colitis, but only 12 per cent of 480 people without the condition. This test couldn’t reveal whether these bacteria were MTB and therefore if they produced aerolysin.

Overall, the studies point to a complex picture. Not every case of ulcerative colitis may involve MTB, and people can also have MTB in their guts without developing colitis.

“We cannot conclude that MTB is the sole cause of ulcerative colitis,” says Zhang. “Persistent MTB infection can induce a hypersensitive state in the colon, but this does not mean that every infected individual will develop colitis.

“The occurrence of colitis in this context is undoubtedly influenced by environmental and genetic factors,” she says.

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There are at least three potential approaches for developing new treatments, says Zhang. One would be to develop drugs that neutralise the toxin. Another would be to develop vaccines targeting either the toxin or the bacteria that produce it. The third would be to use viruses that kill specific bacteria, known as phage therapy, to eliminate the toxin-producing bacteria.

“The case is strong for the MTB toxin disrupting gut immunity by depleting special macrophages in the gut tissue,” says at University Hospital Münster in Germany.

He points out that when the team killed off all gut bacteria in mice, then infected them with MTB, the animals didn’t become more susceptible to colitis. This suggests other, as-yet-unidentified bacteria also play a role.

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“Nevertheless, it may represent an important, missing factor in the multi-step pathogenesis of ulcerative colitis, at least in China,” says Kriegel.

Zhang and her team now plan to do wider epidemiological studies to try to confirm the link between MTB and ulcerative colitis. If MTB infections do play a role and are becoming more common, it might help explain why the incidence of IBD is rising.

The way antibiotics called polymyxins pierce the armour of bacteria has been revealed in stunning detail by high-resolution microscopy, which could help us develop new treatments for drug-resistant infections.

Polymyxins are commonly used as a last-resort treatment against some so-called gram-negative bacteria, which can cause infections such as pneumonia, meningitis and typhoid fever. “The top three World 91ɫ��Ƭ Organization priority pathogens are all gram-negative bacteria, and this is largely a reflection of their complex cell envelope,” says at Imperial College London.

Around their inner cell, these bacteria have an outer surface layer containing molecules called lipopolysaccharides, which act like armour. We knew polymyxins target this outer layer, but how exactly they disrupt it and then kill bacteria wasn’t understood; neither was why the drugs don’t always work.

Now, Edwards and his colleagues have used biochemical experiments and atomic force microscopy – in which a needle just a few nanometres wide creates an image of a cell by sensing its shape – to reveal that one of the two types of polymyxin used therapeutically, called polymyxin B, causes strange bulges to break out on the surface of the gram-negative bacterium E. coli.

Minutes after the protrusions appear, the bacterium begins to quickly shed its lipopolysaccharides, which the researchers detected in the solution it was in.

The researchers say the antibiotic’s presence triggers the bacterium to try to put more and more “bricks” of lipopolysaccharide in its defensive wall. But as it adds bricks, it is also shedding some, temporarily leaving gaps in its defences that allow the antibiotic to enter and kill it.

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“The antibiotics are a bit like a crowbar that helps these bricks come out of the wall,” says Edwards. “The outer membrane doesn’t disintegrate; it doesn’t fall off. But there are clearly gaps where the antibiotic can then get to the second membrane.”

He and his colleagues also uncovered why the antibiotic doesn’t always work: it only affected bacteria that were active and growing. When bacteria were dormant, a state they can enter to survive environmental stress such as nutrient deprivation, the polymyxin B was ineffective, because it wasn’t producing its armour.

However, the researchers found that providing sugar to the E. coli cells woke them from this dormant state and, within 15 minutes, armour production resumed and the cells were killed. The same is expected to apply to the other polymyxin antibiotic used therapeutically, polymyxin E.

Edwards says it might be possible to target dormant bacteria by giving people sugars, but there are dangers to waking these pathogens from their dormant state. “You don’t necessarily want bacteria at an infection site to start multiplying rapidly because that has its own downsides,” he says. Instead, he adds, it might be possible to combine different drugs to bypass the hibernation state without waking the bacteria up.