Extreme responses to uranium exposure

Organisms which are genetically almost identical can exhibit radical differences in behaviour and responses to environmental stress, as a new study from North Carolina State University (NC State) makes clear. The research, reported in Proceedings of the National Academy of Sciences (PNAS) this week, compares two species found in extreme environments.

Metallosphaera sedula and Metallosphaera prunae are both types of Archaea – single-celled microorganisms which contain no nucleus or other organelles – and they share 99.99 per cent of their genetic material. Both are found in highly acidic environments; M. sedula in hot springs near Mount Vesuvius in Italy and M. prunae at the site of an abandoned uranium mine near Thüringen, Germany.

I spoke to Dr Robert Kelly, Alcoa Professor of Chemical and Biomolecular Engineering at NC State, to find about more about the motivations behind the study and what the implications of its findings may be. I began by asking what led Dr Kelly and his team to compare M. sedula and M. prunae.

"We had worked on M. sedula for a number of years – starting in the late 1980s – in relation to the desulfurisation of coal, because it is quite a prolific sulfur-immobilising organism," he told me. 

When Dr Kelly saw an opportunity to apply for research funding related to uranium bioleaching – the extraction of uranium from ore using microorganisms – he recalled the work of a former colleague, Professor Karl Stetter. Based at the University of Regensburg, Professor Stetter had published a paper on M. prunae having discovered it at the site of a disused uranium mine. Dr Kelly thought it would be interesting to compare the effects of the presence of uranium on the two closely-related species.

I wondered if Dr Kelly and his colleagues were surprised by the results of this comparison.

"We compared the two organisms and one proved to be much more resistant than the other," he said. "We had sequenced the M. sedula genome in 2008, and when we sequenced the M. prunae genome we were stunned that the genomes were identical with the exception of around 200 nucleotides. The fact they were responding so differently was unpredictable to say the least."

Whereas M. sedula reacted to the presence of uranium by metabolising it for direct use as an energy source, M. prunae went into a comatose state when faced with pure uranium, effectively shutting down critical cellular processes until the toxic threat was removed. From the close resemblance of the organisms’ genotypes, the researchers have surmised that M. prunae is a ‘spontaneous mutant’ of M. sedula, likely acquiring this singular mutation to help it survive in the environment in which it lived.

Work first started on M. sedula before scientists had the ability to sequence genomes. Dr Kelly believes that this research served to underline the current situation in microbiology, calling into question the way that organisms are classified, or at least the way they were classified in the past.

"Back in those days, you could only tell that one organism was different to another by the way it looked or smelled or grew," Dr Kelly pointed out. "We knew a little about the RNA and DNA, but armed with the genome sequence we realised that even organisms which are virtually the same genetically can have radically different physiological properties.

The potential applications of the knowledge gained are equally diverse. Part of the paper details M. sedula’s prolificacy in directly oxidising uranium from its solid state to a soluble one. Hence, there are some interesting implications for using these types of organisms to recover uranium from ores. However, the team are also working on trying to understand how these organisms resist uranium and why one has a much more effective response than the other.

"We think that heavy metal resistance is probably related to antibiotic resistance mechanisms, so we could get some clues as to how organisms deal with environmental stresses like antibiotics," explained Dr Kelly. "In a sense, uranium is an antibiotic – although of course it would kill the patient as well as the organism – so there could be some common ground between the mechanisms behind the two processes."

As far as further research into these organisms is concerned, Dr Kelly is now aiming to focus in on the finer details.

"We only have to worry about 200 nucleotides out of 2 million, so we’re hoping to track down the genes responsible for the major difference in the way these two organisms operate," he said. "We got lucky in a way because we found two organisms that are almost the same but which behave very differently. Chasing down the differences is now much easier to do than it would be with organisms that are very different genetically."