While much of our attention over the past few years has focused on COVID, a more insidious and dangerous pandemic has spread unabated. This pandemic is about antimicrobial resistance, which is when bacteria evade the antibiotics we use to treat them. You’ve probably heard these bacteria called “superbugs” in the mainstream press.
Read more: We know _why_ bacteria become resistant to antibiotics, but _how_ does it actually happen?
The two main contributors to the emergence and persistence of antibiotic resistance are the mode of action of antibiotics and the ability of bacteria to fight them.
Bacteria are highly evolved life forms that have significant evolutionary advantages over us. One is their doubling time, which for many common varieties of bacteria that infect us is only 15 to 40 minutes.
Also, bacteria grow exponentially, which means that the time it takes for one bacterium to become two is the same as it takes for 100 million to become 200 million.
A consequence of this is that if we kill 99.99% of the bacteria, they can restore their numbers within hours. It is important to note that some or all of these bacteria may be resistant to the agent that originally killed most of their ancestors.
This process of bacterial survival is guided by evolution and the Darwinian principle of natural selection (survival of the fittest), which applies to microorganisms as well as to animals and plants.
How does antibiotic resistance occur?
Almost all current antibiotics work by killing microbes or inhibiting their replication. Bacteria acquire resistance to these antibiotics in two ways: mutation and horizontal gene transfer.
Mutations occur when cells replicate. Some random errors in the replication process can make bacteria better able to evade our treatments.
Horizontal gene transfer is the transfer of genes between bacteria. Most organisms pass genes only vertically, that is, from parent to offspring. But bacteria can swap genes with each other, including genes that allow them to resist antibiotics.
Another disturbing characteristic of current antibiotics is the fact that they are blind. If you take an antibiotic for an infection in your foot, it doesn’t magically go to your foot alone, but is distributed throughout the body, affecting some of the “good” bacteria that live on and in us.
Because of this, many of the 100 trillion bacteria that live in each of us have become resistant to commonly used antibiotics. These “good” bacteria can then transfer resistance to their fellow pathogens.
Read more: Five of the scariest antibiotic-resistant bacteria of the past five years
We need to change how antimicrobials work
In order to control antibiotic resistance, we need to think about antimicrobial therapy in new ways. One of these means is to fight pathogenic bacteria selectively, without killing them.
This may work because most bacteria don’t need to cause disease to survive, and if our treatments aren’t designed to kill them, the selection of resistant mutants will be low and they will be able to continue to live, while in us causing harm.
It may sound fancy, but it is already proving to be effective. For example, there are drugs for urinary tract infections, which do not kill bacteria, but instead target the molecules bacteria need to adhere to the bladder wall. This means that bacteria cannot colonize our bladders and make us sick. But since we’re not trying to kill them, they don’t need to learn how to escape our treatments.
Another approach is to target genes which bacteria need to cause disease, rendering them harmless without killing them.
One of the advantages of antimicrobials that specifically target pathogens is that they don’t affect the “good” bacteria, some of which contribute to our resistance to infection.
A limitation of these types of treatment is that they will have to be specific for each type of bacteria. This means that it will take a lot of time and effort to develop treatments for the many types of bacteria that infect us. However, we know it can be done, since we already do it for viruses (antivirals).
What should happen now?
Until recently, big pharmaceutical companies reacted to antibiotic resistance by developing new drugs to which the bacteria were susceptible. Today, however, few of these companies are interested in new agents. Indeed, it is not profitable to develop traditional resistance-inducing antibiotics, which will become obsolete within a few years.
Read more: Use them and lose them: finding alternatives to antibiotics to preserve their usefulness
As with climate change and other existential threats, antibiotic resistance will need to be fought by governments in collaboration with scientists and industry.
There are other ways to fight bacterial resistance, including vaccines and the proper use of antibiotics. But a coordinated effort that includes these strategies along with specially targeted antibacterial drugs, similar to those currently used to treat viral infections, offers our best hope.
If we don’t act, we face an era that resembles that before the advent of penicillin, where a minor scratch could lead to a deadly infection.