An endolysin is an enzyme that accelerates specific chemical reactions. Its role is to target and break down the rigid cell walls of bacteria. This action compromises their structural integrity and leads to rapid destruction. Think of an endolysin as a precise demolition tool engineered to dismantle bacterial defenses.
The Viral Origin of Endolysins
Endolysins originate from viruses that infect bacteria, known as bacteriophages or simply phages. These viruses are specific, often targeting just one or a few related types of bacteria. A bacteriophage injects its genetic material into a host bacterium, hijacking the cell’s machinery to produce new copies of itself.
Toward the end of this replication cycle, the bacteriophage must escape its host to infect neighboring bacteria. To achieve this, it manufactures endolysins inside the cell. These enzymes accumulate within the bacterium until the virus is ready for release. At a precisely timed moment, the endolysins are unleashed upon the interior of the bacterial cell wall.
The enzymes degrade the cell wall from the inside out, weakening the structure. The wall eventually gives way, causing the bacterium to burst in a process called lysis. This event frees the new phages, allowing them to infect other bacteria and continue the cycle.
How Endolysins Destroy Bacteria
The destructive power of an endolysin is aimed at a specific component of the bacterial cell wall called peptidoglycan. This molecule forms a strong, mesh-like layer that encases the bacterium, providing structural support and protection. The peptidoglycan sheath prevents the cell from rupturing under its high internal turgor pressure.
Endolysins function as molecular scissors, evolved to recognize and cut specific chemical bonds within the peptidoglycan mesh. Most endolysins have a modular structure with two main parts. The cell wall binding domain (CBD) identifies and latches onto a specific molecule on the bacterial surface, ensuring the enzyme is positioned on its target.
Once anchored, the second part, the enzymatically active domain (EAD), carries out the destructive work. This domain catalyzes the hydrolysis, or chemical breakdown, of the peptidoglycan bonds. As the EAD severs these links, it creates holes in the protective mesh. The cell’s structural integrity is compromised, and the internal pressure causes the bacterium to burst and die.
Distinctions from Traditional Antibiotics
The way endolysins kill bacteria is different from that of traditional antibiotics. Most antibiotics work by interfering with a bacterium’s internal functions, such as its metabolism or DNA replication. This process is often slower, requiring the bacteria to be actively growing or dividing for the antibiotic to have a significant effect.
In contrast, endolysins physically dismantle the existing cell wall structure, a direct and rapid form of attack. This lytic action can destroy bacteria within seconds or minutes of contact, regardless of whether the cell is actively dividing. This speed offers a potential advantage in treating acute infections where rapid bacterial clearance is beneficial.
This mechanism also makes it more difficult for bacteria to develop resistance. Bacteria often evolve resistance to antibiotics by altering the specific protein or pathway that the drug targets.
The target of an endolysin, the peptidoglycan structure, is so essential to the bacterium’s survival that significant mutations to it are often lethal to the cell itself. This makes evolving resistance to an endolysin a less likely event.
Therapeutic Development and Applications
The properties of endolysins have led researchers to develop them as a new class of antibacterial agents, sometimes called “enzybiotics.” A focus of this research is their potential to combat antibiotic-resistant bacteria, or “superbugs,” such as Methicillin-resistant Staphylococcus aureus (MRSA). Because endolysins act on the cell wall directly, they are effective against bacteria that have developed resistance to multiple antibiotics.
A challenge in their therapeutic use is the structural difference between types of bacteria. While Gram-positive bacteria have an exposed peptidoglycan layer that endolysins can easily access from the outside, Gram-negative bacteria possess an additional outer membrane. This membrane acts as a barrier, preventing the endolysin from reaching its peptidoglycan target. Scientists are actively working to overcome this by engineering “artilysins,” which fuse the endolysin to other protein components that can disrupt the outer membrane.
Potential applications for endolysin-based therapies are broad. Researchers are exploring their use in topical creams for skin and wound infections, as sterilizing agents for medical devices, and in food safety to eliminate harmful bacteria. Systemic treatments for internal infections are also under investigation, with several candidates undergoing clinical trials to evaluate their safety and efficacy.