/ 7 September 2018

Bug evolution thrown into Chaos

(Graphic: John McCann/M&G)
(Graphic: John McCann/M&G)

Things that have been used to combat bacterial infections: Bread. Honey. Doorknobs. Antibiotics. Viruses. Lasers. And now: an anti-evolutionary mutagenic hand grenade that discourages bacteria from truly expressing themselves.

In the realm of scientific endeavour, evolution and microbiology are familiar bedfellows. Unfortunately the beds they share tend to be in hospital wards, where the mutation of new strains of bacterial infections both help to illustrate Darwinian natural selection in action and cause patients to acquire and expire of infections they didn’t have when they checked in.

Alexander Fleming was awarded the Nobel prize for medicine in 1945 for his discovery of the first true antibiotic, penicillin, in 1928. Shortly after that he told The New York Times: “The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted.”

Narrator: It was not averted.

Staphylococcus aureus can lead to infections ranging from relatively innocuous boils and carbuncles to deadly cases of pneumonia, meningitis and sepsis. Reports of staph becoming resistant to penicillin began to surface as early as 1942. The bacteria were already evolving.

It’s a straightforward application of the Darwinian principle of the survival of the fittest, mixed in with a bit of human nature. An antibiotic treatment might wipe out 100% of a bacterial strain if treatment is thorough, and patients finish their course. But if it isn’t, and they don’t, a tiny portion might survive because a random genetic mutation teamed up with our failure to follow through, and suddenly a new mutated strain emerges stronger than ever, becoming the new normal. The new drug-resistant normal.

READ MORE: Life without antibiotics

Doctors and scientists are acutely aware of the problem. In 2015 the World Health Organisation established Glass— the Global Antimicrobial Resistance Surveillance System, but it has its work cut out for it. Just this week, researchers in Melbourne published a report detailing the emergence of three new deadly variants of Staphylococcus epidermidis in Europe and Australia that are resistant to all known antibiotics.

Closer to home, hospitals have been dealing with cases of drug-resistant tuberculosis since the 1980s. According to Médecins sans Frontières, of the 50000 people around the world who contract the latest strains of multidrug-resistant tuberculosis each year, 1900 of those cases are in South Africa.

As these bacteria mutate and evolve, so too do the attempts to fight them.

Way before Fleming discovered penicillin, ancient Egyptians realised that you could give an injured soldier a fighting chance by stuffing mouldy bread into their wounds. In medieval times, honey was found to be an effective disinfectant.

In the Victorian era, bacterial outbreaks were inadvertently halted because hospital fittings and doorknobs were made of copper, which has since been shown to have antibacterial properties. In 2009 researchers in Kathmandu conducted experiments in which water contaminated with Salmonella and Escherichia coli was added to copper pots. Just four hours later the bacteria in the water in the pot had been eliminated.

To be fair, copper doorknobs might not help much against the super bugs of today. So researchers have been exploring new avenues of treatment, turning their attention to, among other things, bacteriophages — viruses that have evolved specifically to prey upon bacteria — and to the use of lasers during surgery to fry the little bastards out of existence.

And now, researchers at the University of Colorado say they have yoked everyone’s favourite biomechanical tool du jour to the superbug-fighting war wagon.

By employing CRISPR, the gene-editing tool that has revolutionised molecular biology over the past decade, the researchers have created a technique which they claim stops the actual evolution of bacteria in its tracks.

In their study, outlined in Nature Research’s Communications Biology journal this week, the authors call this new technique “the Controlled Hindrance of Adaptation of OrganismS” or Chaos,which is not in the least bit alarming, and certainly does not call to mind Jeff Goldblum’s “Butterfly Effect” comments in Jurassic Park, nor the velociraptored carnage that followed.

Chaos modifies “multiple gene expressions within the bacteria cells, stunting the pathogen’s central processes and thwarting its ability to evolve defences”.

According to the study’s lead author,doctoral researcher Peter Otoupal, tweaking one gene at a time left supercharged Ecoli bacteria still able to adapt and survive. But by really diving in and mucking about with a whole bunch of genes at the same time, the CRISPR-driven Chaos left the bacteria’s genetic code scrambled enough to lead to cascading system failure, making it once again vulnerable to conventional treatments.

“We now have a way to cut off the evolutionary pathways of some of the nastiest bugs and potentially prevent future bugs from emerging at all,” said Otoupal.

Keeping evolution in check is a tall order. But considering that Otoupal’s laboratory has so far failed to be destroyed by a door-opening dinosauror its bacterial equivalent, early indications seem to be that this is a promising line of research that may well yield effective treatments in the field.

Or at least some better doorknobs.