How We Created Superbugs by Provoking Primordial Superpowers in Bacteria

Antibiotic resistance may have evolved before dinosaurs, let alone before doctors began over-prescribing the drugs. But irresponsible practitioners and filthy food workers are still to blame for the current crisis

Image of a bacterium with external pili (filaments), showing DNA and plasmids inside
CI Photos / Shutterstock

Superbugs are terrifying: the spreading scourge of super-STDs springs to mind, such as antibiotic-resistant strains of pneumonia and tuberculosis. People have started to think twice about going to hospital because of the possibility of catching superinfections while being treated for their underlying condition. This April, the United Nations and World Health Organization issued a report urging “immediate, coordinated and ambitious action to avert a potentially disastrous drug-resistance crisis.”

“At least 700,000 people die each year due to drug-resistant diseases, including 230,000 people who die from multidrug-resistant tuberculosis,” the UN writes. 

We can only blame ourselves. We did not create these superbugs, but we have provoked the spread of genetic elements that have existed since time immemorial.

No question: the mounting sense of crisis regarding bacterial resistance is the direct result of antibiotics abuse. However, nonintuitive as it may be, genes for antibiotic resistance turn out to predate antibiotics by millions of years. Bacteria had the genetic propensity to protect themselves from chemicals toxic to them eons before humans and petri dishes evolved. 

If genes against antibiotics evolved not only before the drugs themselves but apparently before the dinosaurs, why has resistance suddenly become a problem? Why are “alarm bells” ringing in scientific corridors?

The dinosaur and the bacterium

Until science actually checked, the assumption had been that antibiotic resistance genes in bacteria evolved after the discovery of the wonder drugs that, naïfs thought in the mid-20th century, would eradicate infectious disease. Well, they didn’t. 

Evolution is based on the propagation of spontaneous beneficial mutations through populations. For us, a generation is, say, 20 years. For some bacteria, it can be 12 minutes to 24 hours. Since bacteria live short lives from our perspective, a mutation can take hold in a bacterial population before our very eyes. 

Bacteria propagate by splitting in two. The resultant two should be identical. It practice, when DNA is replicated, mistakes happen and the two bacteria won’t be 100 percent identical. 

These mistakes are mutations. If the mutations in one are fatal, the individual will die. If they are benign, it won’t (at least, not of that). If the mutations confer an advantage, the bacterium will likely thrive, theoretically outperforming its bacterial peers.  

Thus, administration of a drug that kills bacteria also encourages the development of bacteria with resistance mutations. If an appropriate antibiotic is introduced to the environment of bacteria, they will die. But if that environment has one or two, or a few, variants with resistance to that antibiotic, these variants will not die. They will live and procreate, all other things being equal. And we will get a strain of resistant bacteria — what we call superbugs. 

Given how many bacteria there are and how fast they procreate, humankind assumed their resistance resulted from serendipitous mutations in bugs spurred by the invention of antibiotics. 

Then, in 2011, scientists reported testing 30,000-year-old Beringian permafrost sediments for bacterial DNA. They found it — and, to their surprise, this ancient DNA contained numerous genes encoding resistance to a range of antibiotics. In fact, the structure and function of the gene conferring resistance to vancomycin (an antibiotic used to treat a number of bacterial infections) proved similar to modern antibiotic resistant genes, reported Vanessa D’Costa of Ottowa’s McMaster University and colleagues in Nature.

The very next year, drug-resistant bacteria were found in a cave in New Mexico that had been isolated for some 4 million years. The isolated cave bacteria can resist multiple classes of antibiotics, including new synthetic drugs. “Some strains were resistant to 14 different commercially available antibiotics,” reported Kirandeep Bhullar of McMaster University and colleagues. Horrifyingly, these ancient bugs shrugged off daptomycin, a “last-resort” antibiotic for certain pathogens. 

In 2017, antibiotic resistance genes were reported in staphylococci obtained from the permafrost at Mammoth Mountain in Siberia, dating to the Middle Miocene (around 16 million to 11 million years ago). 

There is yet more evidence. The point is, antibiotic resistance is clearly a natural phenomenon that predates the modern selective pressure of antibiotic use by doctors and vets. The propensity is hardwired into the bacterial genome.

To be clear, don’t assume the scientists were led astray by contamination with modern bacteria in their primordial samples. It bears noting that some scientists claim to have revived actual bacteria that survived millions of years — even 250 million years in one case. The very oldest of these purportedly revived germs were found inside salt crystals. Not all agree that they could possibly be the original creatures, even if they’d been trapped before dinosaurs trampled the Earth. But others think their special suspended animation in salt may have slowed the inevitable DNA decay from radiation.

Whatever the truth about zombie bacteria that predate the brontosaurus, an ancient origin to resistance makes perfect sense. 

Thank fungi

Bacteria have been evolving for billions of years, possibly more than 4 billion years, and over that time they encountered many a source of natural antibiotic. We didn’t invent that wheel, fungi did. Many fungi naturally produce antibiotics, such as penicillin.

Moreover, it turns out that at least some bacteria do have sexual reproduction, and they can “give” one another genes by means of tiny rings of DNA (which aren’t part of the bacteria’s “core” DNA), called plasmids. Wouldn’t you know that these jumping plasmids can carry resistance genes, and often more than one.

When we poisoned ordinary bacterial populations with massive doses of antibiotics, we inadvertently encouraged the expression of this primordial bacterial superpower: resistance to antibiotics. 

Bacteria's internal structure
OSweetNature / Shutterstock.com

WATCH: How bacteria give each other plasmids:

We cooked up the equivalent of the chartreuse-glowing potions that cause these X-Men of the bacterial set to unleash their superpower: surviving antibiotics. 

The same applies to super-fungi that are now starting to raise their deadly heads. A drug-resistant version of a fungal infection called Candida auris is spreading around the world, afflicting chiefly the immune-compromised — and infesting their environment as well. (Israel’s Health Ministry told Haaretz earlier this year that no cases are known in Israel.) The fungus can survive for months in clothing, on furniture, on walls and curtains, books, in ventilation systems. A single patient can shut down a ward. 

What doesn’t kill you makes you stronger, they say. That applies to microbes too. As doctors, vets and farmers lavished antibiotics on an unresisting world, the weaker bacteria died and the stronger ones flourished. Indiscriminate, unnecessary administration of massive amount of drugs turned Earth into a sort of perfect environment for the expression of this ancient trait. Hence the crisis. 

In 2014, the British government — which for all its perceived faults isn’t one to completely ignore bitter reality — predicted that if drug resistance continues to spread, 10 million people could die of superbugs in 2050, compared with “just” 8 million from cancer. This figure was reiterated in the UN report.

The burger flipper and the bug 

How far back resistance goes is likely academic to people harboring resistant syphilis, leprosy or even E. coli, a bacteria that normally lives in our intestines but can become nasty.

In Europe, resistance to commonly used antibiotics against bacteria associated with stomach trouble has more than doubled in 20 years, a paper in Spink Health reported last week.

“Antibiotic-resistant infections correlate with the level of antibiotic consumption,” Sojib bin Zaman of Bangladesh’s International Centre for Diarrhoeal Disease Research and colleagues stated categorically in medical science journal Cureus in 2017

Cultivating resistant salmonella
Elaine Thompson / ASSOCIATED PRE

While we usually blame the proliferation of superbugs on irresponsible practitioners who overprescribe antibiotics and farmers who prophylactically administer drugs to their animals, they have company. Another culprit — at least in the case of E. coli — turns out to be food workers who don’t wash their hands after going to the toilet. Seriously. A team proved that in England, where they did the research, resistant E. coli is “more likely to be spread through poor toilet hygiene than undercooked chicken or other food,” reports the University of East Anglia in The Lancet Infectious Diseases journal. 

Be prepared! But not prophylactic

Apropos antibiotics, it has become common for doctors to recommend that patients follow the therapy with “probiotics,” which isn’t actually a thing; it’s a buzzword for infecting their systems with “good” bacteria (and fungi). Sometimes people take probiotics for no other reason than they think it is beneficial to their well-being. Fortune Business Insights predicts that the global market for probiotics will reach $75 billion by 2025, even though, like vitamin supplements, there are questions about whether these things achieve much. Which begs the question of whether it works.

New research implies that the main beneficiary from this $43-billion-a-year market (in 2017) may be the manufacturers. “It’s a bit like ‘the good, the bad, and the nothing’ — they can do some good, they do a whole load of nothing most of the time, and, as a new study has shown — they can also do a bit of bad,” reported ZME Science, speaking with Israeli scientist Eran Elinav of the Weizmann Institute of Science, Rehovot. 

As Elinav and the team report, ingested probiotics may well colonize the taker’s intestines, but they may overthrow the indigenous microbiome that had been disrupted by the antibiotic — which isn’t necessarily the desired effect.

This fuzziness is why health authorities like the FDA never did approve probiotics as medicines but have left them in the category of dietary supplements. In other words, they’re checked for safety but not efficacy.

What can you personally do about all this? Live sanely. Don’t take antibiotics if you don’t need them is always good advice. Just this week, the American Dental Association stated that antibiotics are not recommended prophylactically for toothaches in most cases, though they are often prescribed exactly for that (just in case there’s an infection lurking that might get worse). Take ibuprofen and get that cavity fixed, the ADA recommends. 

Scientists are working on discovering new antibiotics, to attack resistant bugs with drugs they haven’t encountered before, and there is even thinking about recruiting viruses that attack bacteria, called phages. But meanwhile, don’t give antibiotics to your farm animals or fish or frogs if you don’t have to. If you need and take antibiotics, religiously complete the prescribed course — because if you don’t, you are encouraging the rise of superbacteria: truncated treatment can kill off the weak bacteria, but leave the stronger ones behind.