Antimicrobial Resistance (AMR) is one of the top health threats facing humanity today1.
In 2019 alone, AMR directly killed at least 1.27 million people and contributed to the deaths of almost 5 million people2. This is a problem that affects humans, plants, and animals all over the world and threatens not only human health, but the health of our ecosystems and food supply. This week (November 18th – 24th) is the World Health Organization’s World AMR Awareness Week, which strives to bring awareness to this important issue.
What exactly is AMR, and how does it happen?
AMR is the result of the evolution of microbes (bacteria, fungi, viruses, and parasites) into forms that are no longer affected by drugs we use to kill or weaken them. This can make it impossible to treat or prevent some infections in people, plants, and animals.
Let’s take bacteria as an example.
Bacteria are different from human cells in many ways. One of the biggest differences is that bacteria have a stiff suit of armor around them in addition to their cell membranes. This armor (called the bacterial cell wall) protects bacteria from the environment. Many of our most widely used and effective antibiotics work by disrupting the ability of bacteria to build or remodel their cell walls. However, bacteria are sometimes able to mutate and slightly change specific aspects of their cell walls, thereby making the antibiotics less effective. Bacteria that can still build cell walls even when treated with antibiotics designed to block those processes are called “antibiotic resistant bacteria,” and they contribute to the global AMR crisis.
Schematic representation of a sagittal cut of a pneumococcus bacteria showing different layers corresponding to the capsule, cell wall and cell membrane.
Enter Dr. Josué Flores Kim, who has dedicated most of his research career to studying bacterial cell walls.
The Flores Kim Lab works to understand not only how cell walls are made, but how they are naturally broken down by the bacteria themselves during their normal growth. “Maintaining cell walls when bacteria are rapidly growing and dividing requires a very careful balancing act,” explains Dr. Flores Kim. “Because their cell wall is a complex interconnected meshwork, they have to break down the walls if they want to allow for space to grow and insert new cell wall as bacteria grow and divide.”
Schematic representation of the growth and division process of a pneumococcus bacteria.
The proteins that break down the bacterial cell wall are called cell wall hydrolases or autolysins, and these are the main factors studied in the Flores Kim Lab.
Bacteria must regulate the breakdown of their cell walls with extreme caution – they can’t afford to weaken their armor too much, or else they can’t control their internal osmotic pressure. Too much hydrolase activity breaks down the cell wall and causes the bacteria to explode (a process known as “lysis”), while too little hydrolase activity prevents bacteria from growing and multiplying. If we can learn how bacterial cell wall hydrolases are controlled by bacteria, then hopefully that information can be used to develop new lysis-inducing antibiotics.
To the left, the balance model of cell wall growth in bacteria. On the right a schematic representation of a unbalanced cell wall growth with increased lytic enzymatic function.
Overcoming AMR will require a global effort.
Even though scientists like Dr. Flores Kim and his lab are hard at work trying to discover new antibiotics, AMR is a complicated issue that is impacted by human behavior. Indeed, AMR is primarily driven by the misuse and overuse of antimicrobials (e.g. indiscriminate preventative use of antibiotics in livestock, incorrect usage of antibiotics to treat viral infections, etc)1. If human behavior doesn’t change, it is likely that bacteria will become resistant to all antibiotics that aren’t used responsibly1. While this isn’t the focus of this blog post, it is the focus of World AMR Week. Check out their website to learn more about how to “use antimicrobials prudently and appropriately, take preventive measures to decrease the incidence of infections and follow good practices in disposal of antimicrobial contaminated waste” as we work to prevent AMR together.
