5,000-year-old cave bacteria resist 10 modern antibiotics and carry 600 unexplored genes

Locked inside a 25-meter ice core drilled from a Romanian underground cave, researchers found bacteria that had been frozen since before the Egyptian pyramids were built. When they thawed those bacteria and exposed them to modern antibiotics, the results were striking: the strain resisted 10 of the antibiotic classes routinely used in clinical medicine, including drugs of last resort for serious infections.

The study, published in Frontiers in Microbiology, describes the isolation and characterization of Psychrobacter SC65A.3 from Scarisoara Ice Cave in Romania, home to one of Europe's largest underground glacier formations. The ice core sample that yielded the bacterium came from a layer approximately 5,000 years old.

What ancient resistance tells us about modern antibiotics

Antibiotic resistance is often framed as a consequence of overuse - bacteria evolving in response to selective pressure from medical and agricultural drug use over the past 80 years. This bacterium has never encountered a modern antibiotic. It has been frozen and isolated for 5,000 years. Yet it carries over 100 resistance-related genes and demonstrates measurable resistance to 10 antibiotic classes.

"Studying microbes such as Psychrobacter SC65A.3 retrieved from millennia-old cave ice deposits reveals how antibiotic resistance evolved naturally in the environment, long before modern antibiotics were ever used," said Dr Cristina Purcarea, a senior scientist at the Institute of Biology Bucharest of the Romanian Academy and lead author of the study. Resistance is not a modern invention; it is an ancient evolutionary trait found in environmental bacteria that have never been exposed to pharmaceutical drugs.

The antibiotics it resists

The team tested resistance against 28 antibiotics from 10 classes - drugs used to treat a wide range of serious bacterial infections including tuberculosis, colitis, and urinary tract infections. Resistance was confirmed to rifampicin, vancomycin, and ciprofloxacin - drugs used for severe infections that have limited alternatives when resistance develops. SC65A.3 is also the first Psychrobacter strain found to resist trimethoprim, clindamycin, and metronidazole - antibiotics used to treat urinary tract infections, lung infections, skin and blood infections, and reproductive tract infections.

Importantly, the team first predicted resistance based on genome analysis - identifying specific resistance genes and mutations - then verified those predictions through direct antibiotic susceptibility testing. The match between genomic prediction and phenotypic resistance was strong, validating the genomic analysis approach.

A threat and a resource

The practical concern raised by the study involves climate change. As global temperatures rise, permafrost and glacial ice are melting at accelerating rates. Bacteria like SC65A.3, isolated in ice for millennia, could be released into environments where they can interact with modern bacteria and potentially transfer their resistance genes. The process through which bacteria exchange DNA across species - horizontal gene transfer - means that resistance genes from ancient environmental bacteria could, in principle, spread to pathogens that infect humans.

"If melting ice releases these microbes, these genes could spread to modern bacteria, adding to the global challenge of antibiotic resistance," Purcarea warned.

But the genome also offers potential. The SC65A.3 genome contains nearly 600 genes with unknown functions - an unexplored genetic library that may yield novel enzymes, antimicrobial compounds, or biochemical processes. Analysis identified 11 genes with potential to inhibit the growth of bacteria, fungi, and viruses. The bacterium also demonstrates enzymatic activities with biotechnological potential in contexts including industrial processes and cold-environment applications.

Methodological rigor and limitations

The team took significant precautions against contamination. Ice fragments from the drill core were placed in sterile bags immediately and kept frozen until laboratory processing - standard protocols for ancient environmental microbiology but not infallible against modern environmental DNA. The study characterizes a single bacterial strain; the broader microbial community in the ice core was not fully characterized, leaving open questions about how representative SC65A.3 is of ancient ice cave microbiota.