Antibiotics are an essential type of medicine used to treat and prevent bacterial infections, but their use is threatened by growing levels of antibiotic resistance.
What are the different types of antibiotics, and how do they work? Moreover, how does antibiotic resistance develop and spread?
In this article, I visualize and briefly describe these mechanisms.
By understanding them more clearly, we'll have a better appreciation of how resistance can be a threat; why bacteria might still be susceptible to antibiotics; and how to develop new antibiotics and technologies that can avoid resistance.
Bacteria compete with other bacteria for resources like nutrients and space. Some bacteria produce antibiotics to suppress or kill competitors, giving them an advantage. They target specific processes in bacterial cells that are critical for growth, reproduction, or stability.
Many antibiotics we use today come from nature -- from bacteria that produce compounds to compete with each other -- and we've used this to our advantage. But these bacteria are also in an arms race, and have developed ways to resist antibiotics.
Let's look at these mechanisms more closely.
Different classes of antibiotics target different features of bacteria, as the diagram below shows. For example, beta-lactam antibiotics, like penicillin, block the production of the "peptidoglycan layer", a key component of bacterial cell walls. This weakens the wall, causing the bacteria to burst.
A different example is tetracyclines, which are effective against many Gram-positive and Gram-negative bacteria. Tetracyclines target "ribosomes", which build proteins and are crucial to bacterial growth and survival.
Unfortunately, bacteria can develop resistance to antibiotics. For example, they can produce enzymes called "beta-lactamases" that break down beta-lactam antibiotics. Bacteria can also produce proteins that pump tetracycline antibiotics out of their cells.
To counter this, doctors often prescribe second- or third-generation antibiotics, which bacteria have less resistance to. They could also prescribe combination therapies, which include antibiotics and additional drugs to counter bacterial resistance, such as beta-lactams with beta-lactamase inhibitors. However, over time, bacteria can adapt to these as well.
The diagram below shows four pathways for antibiotic resistance to evolve.
As you can see in the top left of the illustration, bacteria can develop resistance through "de novo innovation" -- like spontaneous DNA mutations or rearrangements. They can also acquire them from other bacteria through "horizontal gene transfer" -- this includes conjugation (direct transfer), transduction (via phages), or transformation (taking up DNA from the environment).
Resistant bacteria can also interact with other bacteria in their environment and shape their evolution. Sometimes, bacteria might be able to also survive if other nearby bacteria produce compounds that help them avoid resistance as well.
Finally, resistant bacteria can migrate between environments or places in the same host.
These mechanisms allow bacteria to adapt quickly and share resistance mechanisms, including between different species.
Resistance mechanisms can also come with costs for the bacteria: for example, producing enzymes like beta-lactamase or maintaining protein pumps can use up energy or resources, which can slow bacterial growth.
If the benefits of surviving antibiotics outweigh the costs, resistant bacteria could dominate over time.
But in some bacterial species, resistance develops slowly, or not at all, due to the costs or evolutionary constraints. For example, group A streptococcal infections are often still susceptible to penicillins.
There are several reasons that bacteria could continue to be susceptible. They might lack the genetic or metabolic ability to produce enzymes, pumps, or other resistance mechanisms without harming their ability to grow and reproduce. Or they might lack the ability to acquire resistance from other bacteria through horizontal gene transfer. These constraints can slow or prevent the emergence of resistance in certain bacterial species.
Although resistance often evolves over days to weeks in labs, it takes longer to evolve in individual people (between days to months) and even longer to spread across populations (between weeks to years).
The arms race between antibiotics and bacteria continues because antibiotics create selection pressure. Bacteria that develop resistance mechanisms are more likely to survive, reproduce, and pass on their resistance genes.
Understanding these mechanisms helps us use antibiotics more effectively by choosing the most effective antibiotics against particular bacteria.
It also helps learn about resistance -- we can see that antibiotic resistance is common and can be shared between bacteria. But antibiotics can still be effective, especially if they're used carefully or if resistance comes with significant costs to bacteria.
Finally, we can learn from the arms race between bacteria and antibiotics in nature, such as by developing new technologies that make it very difficult for antibiotic resistance to evolve.