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 BogotĆ” savannah detected the genome of Treponema pallidum in a human leg bone sample, it was a surprise.

ā€œThis finding was completely unexpected, because the individual studied had no skeletal evidence of a Treponema infection,ā€ 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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ā€œOur results can tell us a lot about the long-term evolutionary history of [this bacterium] by revealing a long-standing association with human populations,ā€ 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 teamā€™s analysis suggests they had many of the same genetic features that make todayā€™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, ā€œmissingā€ 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. ā€œWere there perhaps many extinct lineages and perhaps different diseases caused by these pathogens in the past?ā€ 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.

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. ā€œThe top three World ĪēŅ¹ø£Ąū1000¼ÆŗĻ Organization priority pathogens are all gram-negative bacteria, and this is largely a reflection of their complex cell envelope,ā€ 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 wasnā€™t understood; neither was why the drugs donā€™t always work.

Now, Edwards and his colleagues have used biochemical experiments and atomic force microscopy ā€“ in which a needle just a few nanometres wide creates an image of a cell by sensing its shape ā€“ 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 antibioticā€™s presence triggers the bacterium to try to put more and more ā€œbricksā€ 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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ā€œThe antibiotics are a bit like a crowbar that helps these bricks come out of the wall,ā€ says Edwards. ā€œThe outer membrane doesnā€™t disintegrate; it doesnā€™t fall off. But there are clearly gaps where the antibiotic can then get to the second membrane.ā€

He and his colleagues also uncovered why the antibiotic doesnā€™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 wasnā€™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. ā€œYou donā€™t necessarily want bacteria at an infection site to start multiplying rapidly because that has its own downsides,ā€ he says. Instead, he adds, it might be possible to combine different drugs to bypass the hibernation state without waking the bacteria up.