The human immune system is usually a tireless worker that does its best to keep us protected from pathogen invasion. But even for all of its complexity, there are certain parts of it that fail hard when confronted.
When it comes to combating bacteria wishing to harm us, one of the first actions used by the immune system is to recognize proteins on the surface of the bacterial cell wall or membrane that can help identify it as a threat. If the particular bacteria has been encountered before, then memory T cells can quickly activate the pathways needed to begin producing antibodies and other cellular defenses.
These antibodies need to be particularly tailored to attach to the recognized protein in question in order to act as beacons for white blood cells and other defender cells to destroy the bacteria. With some effort, such antibodies can be made, but they can generally be created to only focus on bacterial proteins and not other molecule types. At least for humans.
For bacteria that use carbohydrates on their membranes instead, it is far more difficult for the immune system to produce the proper antibodies to attach to them. Meanwhile, bacteriophage viruses have found a way around this by creating specialized enzymes known as lysins. These are formatted to bind to carbohydrates in bacterial walls and then cleave open the walls and membranes by breaking down peptidoglycan, a primary structural component.
Upon discovering these specialized enzymes, they have since been used as antibacterial agents and have far fewer issues as compared to antibiotics, since resistance can’t easily form against them. Due to this property, research has long been focused on creating a method of using lysins inside of the body to directly combat bacterial infections. But without special care being taken, the use of lysins could lead to more harm to the patient than help.
A New Antibody
Researchers at Rockefeller University in New York have been investigating these enzymes and also looking into the structure of antibodies. What they noticed is that those two components are not entirely different. They both latch onto particular target molecules (proteins for one and carbohydrates for the other). The main difference is their actions after attaching themselves to a bacterial exterior.
Antibodies start up the immune response and direct other cells to attack the bacteria they are connected to, while lysins themselves cut into the bacteria’s structural peptidoglycan and ultimately kill them. What the scientists found is that they could combine different pieces from each to make a new kind of molecule, one that has the capability to bind to carbohydrates and that has the immune system response abilities.
As an additional experiment, they took a similar carbohydrate focused molecule from bacteria themselves, which use it to reconfigure their own cells walls, and combined that with an antibody, to be able to compare whether such an enzyme from a bacteria or a virus that attacks bacteria will function better.
Taking Out MRSA
For their testing, they focused on particular molecules that bind to Staphylococcus aureus bacteria, as dealing with the dreaded resistance in medical settings of MRSA (methicillin resistant Staphylococcus aureus) is a top priority in medical research. The modified antibodies functioned as desired and attached to S. aureus bacteria and had white blood cells destroy them. Due to the general carbohydrate attachment molecules used, the antibodies were able to attach to several strains of S. aureus and not just the one particular strain that the molecules were obtained for.
Their experiment even suggested more distantly related bacteria might be able to become targets for the modified antibodies. In a test against MRSA, the researchers also found that the test mice with the antibodies had a significantly higher survival rate as compared to the control group without them.
The scientists decided to dub these modified antibodies with lysin components as ‘lysibodies’. Human testing has already been started and they hope to have these modified antibodies available for public treatment in only a few years time.
Next Step For Immunology?
In addition to the hope that these created antibody-like systems will be able to improve human and animal health prospects against bacteria, the scientists also wish to try out other combinations of binding molecules with antibodies, to see if they can be used against not just bacteria, but also viruses and fungi.
If they are successful in that extended endeavor, then the field of immunology is going to become quite interesting indeed.
Photo CCs: Staphylococcus aureus VISA 2 from Wikimedia Commons