Bacteria are one of the most common causes of human infection. Since the discovery of antibiotics nearly 90 years ago, bacterial infections have been largely treatable. Antibiotics have saved millions of lives and have extended life expectancy by roughly two decades in most countries across the globe. However, as bacteria have been exposed to more and more antibiotics, they have begun to develop resistance against them. As a result, our world is currently facing a mounting threat that has been referred to by the World Health Organization (WHO) and the Centers for Disease Control (CDC) as a post-antibiotic era, wherein simple infections that were once treatable, will become untreatable with traditional antibiotics. The CDC has estimated that 2 million people become infected with antibiotic-resistant bacteria in America each year. Of those, 23,000 die because antibiotics fail to save their lives. The concern is that these numbers are on the rise.
In the past few decades, scientists have discovered an additional aspect about bacteria that has helped us understand how they develop resistance to antibiotics. Bacteria can be found in every environment and location on Earth; from the deep ocean floor, to the highest mountaintop. Bacteria also dwell in and on our bodies. In fact, our bodies have more bacterial cells than our own cells. To protect themselves in these environments, bacteria group together to form communities that contain millions or billions of bacteria. In a community, bacteria “talk” to one another, share genetic information and encapsulate themselves in a sticky matrix called exopolysaccharide substance (EPS) that stores nutrients, water and provides protection. These communities of bacteria are known as biofilms.
Biofilms are hardy. They are much more resistant to antibiotics compared to planktonic bacteria, i.e. bacteria that float freely in an environment such as river water. Many of the superbugs that are talked about in the news, such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), vancomycin-resistant enterococci (VRE) and others have the ability to form biofilm communities.
Biofilms typically grow on solid surfaces. We encounter biofilms every day of our lives. For example, we brush our teeth to remove biofilms—more commonly referred to as plaque. Rocks in river water become slippery because biofilms grow on them. Biofilms are also what cause rings to form in our bathtubs and toilets in our homes if not cleaned frequently and effectively. In almost every environment on Earth, the large majority of bacteria prefer to live in these biofilms rather than alone as planktonic cells.
Biofilms can also cause severe infections in our bodies. Tuberculosis, Lyme disease, medical device-related infections, osteomyelitis, chronic skin wounds and infections that accompany cystic fibrosis are all examples of biofilm-related infections. Infections caused by biofilms can be much more difficult to treat than infections caused by planktonic bacteria. These infections may become chronic and often do not respond to antibiotics, or they recur when antibiotic treatment is stopped.
Several factors contribute to a biofilms’ ability to resist antibiotic treatment. For example, bacteria in a biofilm can exchange genetic information, which codes for proteins that block the effect of antibiotics. Water channels are also formed in a biofilm community that shuttle antibiotics away from the bacteria. Lastly, deep in the biofilm community, oxygen becomes less available creating an anaerobic environment that causes cells to go into a dormant, or sessile state. Antibiotics do not affect these cells because they are more effective against bacteria that are metabolically active. These cells become resistant variants and as they mature, they become more difficult to kill and a source of severe infection.
The combination of these factors makes biofilms highly resistant to traditional antibiotic treatment and thus a major contributing factor to the worldwide threat of antibiotic resistance.
For this reason, Curza is developing a first-in-class series of antibiofilm antibiotics that are specifically targeted toward killing and eradicating bacteria in the biofilm phenotype. No antibiotic has been developed previously with this specific intent. Curza is the world leader in the development of antibiofilm antibiotic technology and is dedicated to protecting our world from the harmful, even life-threatening effects of biofilms.