In northern China, where the Gobi Desert meets the Tibetan Plateau, lies a vast expanse of rippling sand dunes, mountains, and bare rock. Winters here are long and harsh, with temperatures sinking below –25 degrees Celsius, and rainfall is so sporadic that only well-adapted species are able to survive. For decades, researchers have ventured here to search for life that can exist in this hostile environment.
Recently they’ve been hunting for something in particular. Scientists believe that organisms that live in tough environments could help combat the urgent and ever-growing threat of antibiotic-resistant bacteria, which are becoming increasingly deadly. The first comprehensive assessment of their impact, released earlier this year, estimates that drug-resistant bacteria directly killed over a million people in 2019 and played a part in the deaths of several million more people that year.
One way of countering this threat is to find new antibiotics—substances that bacteria haven’t had a chance to become resistant to—and bacteria themselves are a good source for these. Many drugs we use today are substances that bacteria produce to protect themselves from other microbes. Lots of research therefore focuses on finding new bacteria with antimicrobial properties—hence trekking into the desert.
“The idea is that the more extreme the conditions, the more the organisms that exist are going to be forced to evolve and adapt,” says Paul Dyson, a molecular microbiologist at Swansea University Medical School in the UK. Where tough conditions mean high competition for survival, you’ll find bacteria that produce stronger defenses against their rivals, the theory goes.
And in the depths of the desert, Dyson and his collaborators at the Chinese Academy of Sciences have discovered a species of bacteria that does indeed have an edge—and could transform the process of antibiotic discovery itself.
In 2013, Dyson’s Chinese colleagues isolated a previously unknown species of Streptomyces bacteria they had discovered in the far south of the Gobi Desert, in a region called the Alxa Plateau. After sequencing the bacterium’s genome, they found that it not only produced antibiotics that killed other bacteria, but that it was also extremely fast growing compared with already-known species of Streptomyces.
Sequencing also revealed that this desert bacterium possessed a never-before-seen gene for transfer RNA (tRNA). This is a molecule that allows organisms to read their genetic material and, by doing so, build the other molecules they need to exist. Dyson and his team soon detected that this newly discovered tRNA gene triggered the molecular switches that control antibiotic production much more efficiently than in conventional antibiotic-producing bacteria.
Many of the most medically important bacteria belong to the genus Streptomyces: a group that includes more than 500 known species. These are so widely found in the ground that molecules produced by Streptomyces are what gives soil its characteristic earthy smell. More importantly, Streptomyces are a vital source of medicine. Over two-thirds of naturally occurring antibiotics used today are derived from this bacterial group.
And there are undoubtedly many more bacteria out there that could give us useful new antibiotics to use. But if you find what appears to be a promising one, the next step is to coax it into generating sufficient quantities of antibiotics for analysis—and this can be a real challenge.
Antibiotic discovery is “often hindered by low yield,” says Laura Piddock, scientific director of the Global Antibiotic R&D Partnership (GARDP) in Geneva. Plus, sometimes a bacterium will have the potential to produce useful substances, but “the genetic machinery is turned off, so no antibiotic is made,” Piddock adds.
Knowing this, Dyson and his collaborators decided to take the tRNA gene from the fast-growing desert bacterium and add it to conventional Streptomyces bacteria already used to make clinical antibiotics. The team’s hypothesis was that the gene from the fast-growing bacterium would supercharge these other bacteria’s antibiotic production—which is exactly what happened. The modified bacteria produced antibiotic compounds in two to three days—around half the time it usually takes conventional Streptomyces species.
These findings, published in the journal Nucleic Acids Research, could be highly useful in the quest for new treatments. If scientists find a new bacterium that appears to generate something that could be used as a medicine, but doesn’t produce very much of it (as is often the case), there’s a tool to potentially make it much more productive. “I strongly believe this is a very simple strategy to be integrated in any new antibiotic discovery program,” says Dyson.
Piddock agrees. Getting bacteria to produce greater volumes of antibiotic substances “will be of much interest to researchers in this field” and have a positive impact on human health, she says. “This should enable them to discover new antibiotics that could form the basis of new drugs to treat infections.”
This is good news, as right now the World Bank estimates that antimicrobial resistance (AMR) is one of the biggest threats to global health, food security, and development. According to an alarming 2019 UN report, if no action is taken to combat these pervasive superbugs, 10 million people per year could die from drug-resistant diseases by 2050. Concerningly, the increased use of antibiotics during the pandemic (to protect Covid-19 patients from secondary infections) has seen drug resistance rise.
Resistance happens when bacteria are repeatedly exposed to antibiotics and evolve ways to withstand them. The phenomenon is exacerbated and accelerated by misusing and overusing antibiotics in both humans and livestock—including when humans take antibiotics for viral illnesses (they only work against bacteria) and when otherwise healthy livestock are given them for disease prevention.
“It is impossible at any point to completely stop AMR, as it’s a natural phenomenon, but the rate and the threat can be mitigated and controlled,” says Hatim Sati of the Antimicrobial Resistance Division at the World Health Organization.
Dyson’s desert bacterium is one species that could help, but there are plenty of others adapted to extreme environments that could also offer a way out. Dubbed extremophiles, such organisms have been isolated from some of Earth’s most inhospitable places: submarine volcanoes, deep-sea sponges, and amid the sands of the driest place on earth. These habitats have intensely high or low temperatures, pH, pressure, or salinity, or combinations of all of these.
A few years ago, Dyson was part of another team that discovered several novel species of Streptomyces in the Boho Highlands in Northern Ireland, an area known for its biodiversity. The landscape is made up of limestone, highly acidic bogs, and alkaline grasslands, and the challenges of these features—as in the Gobi Desert—offer a unique environment for tougher bacteria to potentially evolve. For centuries, the land—which was occupied by Druids 1,500 years ago—has held a mystical reputation, with the soil especially known for its healing and curative powers, often used in tinctures and to treat wounds.
Gerry Quinn, a scientist on the team who used to live in Boho, says that his great uncle was a local healer in the area and was known to hold the cure for several ailments. “There were always tales of people who had the ‘cure,’” says Quinn. “It was really a closely guarded secret of a medicine passed down from one generation to the next, with very strict rules. You couldn’t sell the cure, you couldn’t trick the person seeking the cure, and you had to make it exactly as you were taught.”
Recalling such lore, Quinn returned to the land where he used to gather hay and instead gathered samples of bacteria. The scientists discovered that one of the strains of bacteria, which the team named Streptomyces sp. myrophorea, was able to combat four of the top six antibiotic-resistant pathogens, including MRSA.
It’s important to note that the discovery of these microbes is only the first of many steps in developing new antibiotic drugs. Very few newly discovered substances will end up becoming a medication, whether because of their toxicity to humans or a variety of other factors. And even once those hurdles have been jumped, years of clinical trials follow.
Still, Dyson is hopeful that the key to overcoming AMR is out there in nature, and that with the newly discovered tRNA gene, scientists will be able to make the most of what comes to light. For now, though, the search for promising bacteria continues—meaning that researchers will keep venturing out into Earth’s most extreme environments.
