Humanity’s uphill battle against antibiotic resistance

By: Zuri Sullivan

Antibiotic resistance is a public health crisis that has received lots of attention recently, and for good reason. One only need read Maryn McKenna’s essay in Medium to understand the gravity of the situation. The advent of antibiotics in the 20th century, in addition to improvements in sanitation and other medical advances, saw a doubling of life expectancy in the United States. If widespread antibiotic resistance were to render these miracle drugs virtually useless, we could return to the dismal reality of our grandparents’ childhood, where apparently innocuous infections like strep throat could spell a death sentence.  And for every antibiotic currently on the market, there exist bacteria that are resistant to it.

So how does antibiotic resistance arise? The emergence of antibiotic resistance is actually a real-time illustration of evolution. When Charles Darwin published On the Origin of Species in 1859, he put forth the theory of natural selection, which became the basis for what we now call evolutionary biology. The basic principle is as follows:

  • Variation arises amongst organisms due to random genetic mutations
  • The environment that organisms are exposed to determines whether this mutation is beneficial (makes them more fit, or able to reproduce) or detrimental (makes them less fit)
  • When a mutation confers a fitness benefit, the organisms that possess this mutation reproduce more, passing down the variation to their offspring
  • Thus, over generations, beneficial mutations become more frequent in the entire population

Antibiotic resistance is an example of a variation that could arise in a population of bacteria. When the population is exposed to antibiotics, this mutation confers a fitness benefit to the mutant. The antibiotic kills the non-mutant bacteria, while the mutant survives, and gives rise to mutant offspring. Not only can resistant bacteria spread antibiotic resistance genes to their offspring, but they can also pass them to their neighbors through a process called horizontal gene transfer. Over time, the entire population of bacteria becomes resistant to the antibiotic. When this happens inside a person’s body, it can mean that the drugs that their doctor prescribes to treat an infection may not be effective.

The gravity of the situation is clear—antibiotic resistant infections account for about 23,000 deaths per year in the US alone, and are estimated to cost us as much as $35 billion annually. Though the problem is obvious, the solution is much less so. Many have been proposed, from restricting the use of antibiotics in agriculture, (the vast majority of antibiotics sold in the US are bought by the agriculture industry), limiting the inappropriate use of antibiotics in medicine, to reducing antibiotic treatment regimens to the lowest level possible to improve a patient’s health. The most obvious solution, and the one scientists have been working on since antibiotic resistance was first described in 1940, is discovering new antibiotics.

Unfortunately, this endeavor has produced limited success. In the past 50 years, there has only been one new class of antibiotics introduced into clinical practice; the overwhelming majority of antibiotics developed in the last several decades have been variations on existing compounds. And for most new drugs, resistance arises so quickly that antibiotic-resistant bacteria can be detected in the population years before the antibiotic even hits the market. It would seem that humans are fighting a losing battle against bacteria.

A glimmer of hope came earlier this year, when researchers from Northeastern University published a study in Nature describing the discovery of a new antibiotic without detectable resistance. The new compound, teixobactin, was found to be effective against a number of disease-causing bacteria, including Staphylococcus aureus (staph) and Mycobacterium tuberculosis (TB). Not surprisingly, this discovery generated a lot of excitement in the scientific and medical communities. But some wonder whether the development of resistance against new and exciting drugs is just a matter of time.

The answer could come from a surprising source: bacterial DNA isolated from the remains of woolly mammoths, massive, now-extinct relatives of modern elephants who walked the earth during the Pleistocene Epoch over 30,000 years ago. A 2011 study in Nature described the detection of bacterial antibiotic resistance genes in samples isolated from woolly mammoths and other ancient animals from the Pleistocene. Based on what I’ve told you already, this seems crazy. After all, antibiotic resistance is driven by the use of antibiotics, and humans have only been using antibiotics for about 100 years. So why would bacteria from 30,000 years ago be evolving resistance to antibiotics?

It turns out that humans weren’t the first organisms to realize that antibiotics are a good way to kill bacteria. Bacteria themselves were the original inventors of antibiotics, and they’ve been using them to kill each other for millions of years. That’s right—our modern antibiotics are the product of millions of years of interbacterial warfare. Humans only discovered antibiotics in the 20th century, but bacteria have been using them for much longer than that. For as long as these weapons have existed, their targets have been devising ways to evade them. If resisting antibiotics is a fundamental component of what it means to be a successful bacterium, can antibiotic resistance ever really be eliminated?