It has been named Psychrobacter SC65A.3 and was found buried under meters of ice in a cave in Romania. It had been entombed for some 5,000 years and, despite this, appears to be resistant to a dozen modern antibiotics. Its discoverers have also found that it inhibits the growth of other bacteria, including some of the most difficult-to-treat pathogens. The research, published in the scientific journal Frontiers in Microbiology, delves into its genetics to explain how a bacterium can be both drug-resistant and a potential antibiotic against others.
“Species of the genus Psychrobacter are exceptionally cold-resistant bacteria that thrive in extreme environments such as polar sea ice, glaciers, permafrost, and the deep ocean,” says Cristina Purcarea of the Institute of Biology in Bucharest and senior author of this research. “Their ability to survive and adapt to diverse icy habitats indicates the extraordinary resilience of these microbes,” she adds. “However, the particular strain we recovered from the Scarisoara glacial cave is unique, as demonstrated by the limited DNA identity score with homologous Psychrobacter species.” This low percentage of genetic sequence matching with its closest relatives provides clues to its specificity.
The Scarisoara Cave in the Romanian Carpathians is like a giant natural freezer. It houses one of the world’s largest underground glaciers, with an ice block of approximately 75,000 cubic meters. There, the stalactites and stalagmites are a strange mixture of ice and calcite. From one of its chambers, researchers extracted a 25-meter-long ice core, dating back some 13,000 years. At a depth of 16.5 meters — corresponding to 5,335 years ago according to carbon dating — they found an entire bacterial ecosystem, with microorganisms likely active, not dormant. As their name suggests, Psychrobacter are psychrotrophic organisms, adapted to the coldest environments on the planet.
Analyzing the resistance of the SC65A.3 strain to 28 antibiotics from 10 classes used to treat bacterial infections, researchers found it was resistant to a dozen of them, some broad-spectrum and others specific, such as clindamycin, lincomycin, and vancomycin. “The 10 antibiotics we found resistance to are widely used in oral and injectable therapies to treat various serious bacterial infections in clinical practice,” Purcarea explains. The growing resistance to antibiotics threatens to kill millions of people.
How can a bacterium that has lived for 5,335 years under 16.5 meters of ice in a remote cave in the Carpathian Mountains be resistant to antibiotics developed only a few decades ago? “It’s not resistant to modern drugs because it came into contact with them, but because evolution had already equipped these microbes with mechanisms to survive chemical threats long before humans invented antibiotics,” says the Romanian scientist. For millions of years, bacteria have had to fight other bacteria and microorganisms, especially fungi, to survive, a struggle that has left its mark on their genetics, “and these same genes can also confer resistance to the antibiotics we use today, even though they are relatively recent,” Purcarea adds.
Iñaki Comas, head of the Tuberculosis Genomics Unit at the Institute of Biomedicine of Valencia/CSIC, shares this view: “The vast majority of genes related to antibiotic resistance had or have other functions and have always existed.” Comas, who was not involved in this research, adds that “bacteria have been fighting fungi or each other throughout their evolutionary history, and the way they do this is by resisting attacks from others. And what are those attacks? All antimicrobial ones.” Hence their own potential as antibiotics.
The same mechanisms that point to resistance are what make Psychrobacter SC65A.3 such a tough organism to crack. When cultured in the lab and exposed to 20 clinical pathogens, it was observed to inhibit the growth of most of them. Some of these are among the most resistant and feared bacteria, such as Staphylococcus aureus, generally benign in healthy individuals but the worst hospital-acquired infection, and several strains of Escherichia coli. It also showed remarkable antibacterial activity against Enterobacter spp, and three strains of Klebsiella pneumoniae.
“The cave strain showed an impressive ability to combat 14 harmful pathogens from the well-known ESKAPE group,” explains Purcarea in an email. This group includes the six most dangerous antibiotic-resistant microbes, according to the World Health Organization’s definition. “This potent antimicrobial effect is likely due to genes that produce natural antibiotic compounds, highlighting its potential as a source of new treatments,” the researcher concludes.
Sara Hernando-Amado, principal investigator at the National Center for Biotechnology (CNB-CSIC), who was not involved in this research, points out that one limitation of the study is that “Psychrobacter is an environmental bacterium, for which there are no clinical breakpoints. The authors manage this by using Acinotabacter (genetically closely related) and less phylogenetically related bacteria as a reference.” These breakpoints (EUCAST breakpoints) are reference values used to determine whether a microorganism is susceptible (the antibiotic works) or resistant (the drug does not inhibit bacterial growth). The lack of reference values for this microorganism is a weakness acknowledged by the study’s authors, which means that the discovered multidrug resistance must be considered with caution.
On the other hand, Hernando-Amado adds that “the intrinsic resistance of many bacteria (including environmental ones) to antibiotics and their ability to evolve rapidly and acquire higher levels through mutation is well known, so the key lies in understanding this process and exploiting bacterial Achilles’ heels associated with resistance.” This could allow for the rational use of antibiotics, “combining antibiotics where the use of one increases sensitivity to the other, for example,” she adds. Despite the limitations, the discoverers of Psychrobacter SC65A.3 are already searching for the specific biomolecules responsible for its antimicrobial potential.
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