Faced with an onslaught of new, drug-resistant superbugs, determined scientists are venturing into the depths of the Earth in search of rare and unusual bacteria that may form the basis of tomorrow’s antibiotics.
…the true function of such metabolites in nature may be to act as a form of language between bacteria, enabling them to communicate and actually share resources. In a cave, this is particularly vital. After all, as Cheeptham points out, “[In a cave habitat] is it better for them all to compete and die, or to live together in co-operation?”
Contrary to common misconception, human beings have not developed a resistance to antibiotics through overexposure. Instead, the bacteria themselves have evolved to evade our methods of killing them. We have, according to Cheeptham, around 1.3 kilograms of bacteria in and on our bodies at any one time. Their mass is roughly the equivalent to that of the human brain and, despite what domestic kitchen cleaners and soaps would have you believe, 99.9 per cent of all bacteria are actually neutral or beneficial to our health.
“Previously, we thought that overuse and misuse of commercially available antibiotics caused resistance in bacteria,” Cheeptham explains. “But the truth is that we train them. When bacteria see triclosan [an antibacterial agent found in cleaning products, soap and toothpaste] coming towards them, they want to live, like all life on Earth. Most will die, but some figure out defence mechanisms that help them survive, such as creating a pore in their cell wall to allow them to pump out the drug faster than it comes in.” She taps her finger on the table to emphasis a point that she is clearly still in awe of. “Bacteria are smarter than us.”
This isn’t the only revelation that has changed the way researchers look at bacteria. “We’ve known since 1928 that bacteria produce both asexually and sexually, but we didn’t really make the connection between the latter method – also known as ‘horizontal gene transfer’ – and the passing on of antibiotic-resistant genes until very recently,” Cheeptham explains.
Cheeptham and her colleagues reported cataloguing 100 bacteria isolates in the Iron Curtain Cave. Of these, 12.3 per cent were unknown, and may even be completely new bacteria. So far, two of them have proved to be efficient against multi-drug-resistant microbial strains.
The first time Naowarat Cheeptham ventured down into the Iron Curtain Cave, one day in 2011, the darkness was all-consuming. Turning away from the steel ladder – the only route back to the small square of sunlight far overhead – the biologist forced herself to continue forward.
Cheeptham, 48, who is known by her friends as Ann, did not stumble upon the Iron Curtain herself. The cave, located in the hills of Chilliwack, in British Columbia, Canada, were discovered in 1993 by Rob Wall, a local construction contractor and amateur caver. Wall was exploring the hills in search of uncharted caverns he might open up and explore for his own pleasure. A great deal of caves in this area of Canada are actually closed sinkholes. As such, Wall’s search involved a process called, unsurprisingly, digging, in which promising, sunken areas of ground are excavated. One day, Wall was walking through the woods and tripped into such a hole. He returned the next day with a friend and a shovel. The pair dug for three hours, uncovering a hole ten metres deep, with two small rooms at the bottom. It was everything Wall had been looking for.
It wasn’t until six months later, in the autumn of 1993, when Wall was showing off his discovery to a group of friends, that one of them noticed a breeze blowing through from the back of the cave. The group investigated, shifting rocks until they opened up an entrance to half a kilometre of pristine caves. The underground network shone with gypsum crystal, the walls and floor bristling with stalagmites and stalactites. Not human being had been there before. “It was beautiful,” Wall says.
Wall was approached by Cheeptham in 2011. The biologist was on the lookout for local caves to explore and Wall invited her to give a presentation to the Chilliwack River Valley Cavers (CRVC), explaining her project. Cheeptham explained that the dark, dank subterranean caves are teeming with life in the form of largely uncharted extremophiles – organisms that thrive in conditions that would be geochemically hostile to most life forms on earth. For Cheeptham and her colleagues from Thompson Rivers University Department of Biological Sciences, spelunking in search of these extremophiles is no mere hobby, but a last-ditch attempt to find a solution to one of the biggest global threats facing humanity today: antibiotic resistance.
While extremophiles are not the only avenue in the search for new antibiotics, their ability to not only survive but thrive in habitats where other bacteria would die suggests their chemical secretions are particularly potent. Caves are a rich source of less-studied bacteria because of their natural biodiversity, and seclusion from other environments in which bacteria usually develop.
It is not actually the bacteria themselves that are used to make antibiotics, but their metabolites – chemical compounds produced by them as a by-product of their growth. Yeast’s metabolite, for example, is the result of fermentation. It was once thought that some of these metabolites existed to kill off competing bacteria. However, new thinking popularised by a number of biologists, including Julian Davies at the University of British Columbia, argues that the true function of such metabolites in nature may be to act as a form of language between bacteria, enabling them to communicate and actually share resources. In a cave, this is particularly vital. After all, as Cheeptham points out, “[In a cave habitat] is it better for them all to compete and die, or to live together in co-operation?”
After watching Cheeptham’s presentation, local caver Doug Storozynski, 51, volunteered to help her explore the local caves. While not as technically challenging as other caves in the vicinity, the Iron Curtain still contains its share of tight squeezes, and requires an experienced guide to navigate safely. When they descended into the gloom, Cheeptham felt, at first, claustrophobic and scared. But as she and her team ventured deeper through cramped crawl spaces, numbing underground waterways and abrasive rock walls, their way lit by head-torches, the cave came alive. Stalactites hung from the ceilings, stalagmites rising from the ancient floor.
Bacteria inhabit secondary mineral deposits in the form of soda-straw speleothems – natural calcium-based deposits which include stalactites and stalagmites. After 15 minutes of feeling their way along in the near-dark, Cheeptham and her team reached the back wall of the cave, where a cascade of red-tinged, curtain-like limescale deposits give the cave its name. Next to this wall, the ceiling sloped down into the darkness of a side recess. It was the 60-centimetre stalagmites hanging from this ceiling that Cheeptham targeted. As the blue-grey caverns took shape, Cheeptham’s trepidation was replaced by curiosity and excitement.
Crawling into position, she knelt in the small space between floor and stalagmite and retrieved the sample kit from her rucksack. With sterile forceps she scraped away a near-minuscule section from the tip of the first stalagmite, dropping it into a 50ml Falcon Tube before securing it away. She worked quickly by the light of her head torch, filling her half-dozen containers with stalagmite samples. The team then retraced their steps back to the surface. Cheeptham deposited the samples in the coolbag designed to keep the bacteria alive until they could be analysed in her lab.