How does antibiotic resistance come about?
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 may make bacteria better able to evade our treatments.
Horizontal gene transfer is the transfer of genes between bacteria. Most organisms only pass on genes vertically – that is from parent to offspring. But bacteria can exchange genes among themselves, including genes that enable them to resist antibiotics.
Another worrisome feature of current antibiotics is the fact they are indiscriminate. If you consume an antibiotic for an infection in your foot, it does not magically go to your foot alone, but is distributed throughout the body, affecting some of the “good” bacteria that live on and in us.
For this reason, 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 disease-causing companions.
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 ways is to tackle disease-causing bacteria ively, without killing them.
This can work because most bacteria don’t need to cause disease in order to survive, and if our treatments aren’t designed to kill them, the ion for resistant mutants will be weak, and they can go on living, while causing us no harm.
This may sound fanciful, but it is already proving effective. For example, there are drugs for urinary tract infections, that do not kill the bacteria, but instead target the molecules the bacteria need to stick to the bladder wall. This means the bacteria can’t colonise our bladders and make us sick. But as we are not trying to kill them, they have no need to learn to evade our treatments.
Another approach is to target the genes bacteria require to cause disease, making them harmless without killing them.
An advantage of antimicrobials which target pathogens specifically is that they won’t affect the “good” bacteria some of which contribute to our resistance to infection.
One limitation of these types of treatment is they will need to be specific for each type of bacterium. This means it will take significant time and effort to develop treatments for the many different types of bacteria that infect us. However we know this can be done, since we already do it for viruses (anti-virals).
What has to happen now?
Until recently, major pharmaceutical companies responded to antibiotic resistance by developing new drugs to which bacteria were susceptible. Now, however, few such companies are showing interest in new agents. This is because it isn’t cost-effective to develop traditional, resistance-inducing antibiotics, which will become obsolete within a few years.
As with climate change and other existential threats, antibiotic resistance will need to be tackled by governments in collaboration with scientists and industry.
There are other ways to combat bacterial resistance, including vaccines and ensuring antibiotics are used appropriately. But a coordinated effort comprising these strategies together with specially targeted anti-bacterial drugs, similar to those currently being used to treat viral infections, offers our best hope.
If we don’t act, we face an era resembling that before the advent of penicillin when a minor scratch could result in a fatal infection.
