Our medical system is at a crisis point. Bacteria that we could once easily dispatch are out-evolving our current antibiotics, leading to the growth of "superbugs."
The Review on Antimicrobial Resistance found that 700,000 people per year currently die of infections that have developed a resistance to our current antibiotics. That number is expected to swell to 10 million per year by 2050, making the search for new antibiotics or alternatives to the drugs urgent. Now, reports Layal Liverpool at The Guardian, early tests on a new type of drug called an immunobiotic, which combines the power of antibiotics and the human immune system, is showing promise.
The idea comes from the world of cancer therapy, where a suite of recently developed immunotherapy techniques boost the body's natural ability to fight off cancer cells. For the new study in the journal Cell Chemical Biology, researcher Marcos Pires of Lehigh University and his colleagues combined an existing antibiotic with a protein which stimulates the immune system to attack. According to a press release, the new study builds on past research from Pires and his team. In the past research, they placed antigenic epitopes, the part of bacteria that is recognized by the immune system, on Gram-postitive bacteria, a broad class of bacteria that are generally susceptible to antiobitics. The epitopes flagged the bacteria, triggering white cells and othe immune fighters to attack.
In this study, the team wanted to flag Gram-negative bacteria, which have a tougher cell wall and include difficult-to-treat infections like E. coli and Pseudomonas aeruginosa, which can cause pneumonia. To do that, they combined a current antibiotic called colistin with those immune-system-stimulating epitopes. In essence, the combo is a one-two punch to the bacteria. “To target these bacteria, we turned to an old class of antibiotics known as colistin,” Pires says in the press release. “Colistin is a last-resort antibiotic. It just so happens that it destroys bacteria by landing on its surface. We modified colistin with an agent that attracts antibodies onto the surface of the bacteria and built a compound that both directly kills bacteria and at the same time induces an immune-response.”
The team then studied the “immunobiotic” on several types of difficult-to-treat bacteria grown in human serum, which is part of blood. While the drug attaches to molecules on the surface of bacteria cells, the same molecules do not exist on human cells, meaning the drug should not have any toxic effects. In the study, the drug destroyed many of the types of bacteria, including Pseudomonas aeruginosa and E. coli, and without impacting the human cells. When it was tested on nematode worms infected with the bacteria, the researchers found the same results.
The team then tested the new drug in combination with older antibiotics, which many bacteria have become resistant to. In those cases, it appears the new drug increased the effectiveness of the older drugs, resensitizing the resistant bacteria to the antibiotics.
The advantage of such a system is that bacteria, which can mutate to develop resistance to drugs, can't as easily evolve defenses against the human immune system. “The idea of using a molecule which targets the outer membrane of bacteria to enhance their responsiveness to drugs or antibodies is very attractive,” Tim McHugh, director of the University College London Centre for Clinical Microbiology, tells Liverpool. “Bacteria are less likely to become resistant to drugs that target the immune system compared with drugs that target the bacteria more directly.”
In future work, the team hopes to refine their drug and test it on more complex animals. If "immunobiotics" don't pan out, there is still some hope for a bug-free future; other teams are also working on alternatives to our failing arsenal of antibiotics. Earlier this year, a team at the University of Lincoln successfully synthesized a new class of antibiotic capable of dealing with some of the superbugs that are beginning to develop around the world. Researchers have also recently found a new antibiotic by sequencing the DNA of over 2,000 microbes living in dirt.
The new treatments can't come soon enough. In just the last two decades, global antibiotic use has increased by 40 percent. The misuse and overuse of the drugs, which is unlikely to stop soon, cause the mutations which lead to superbugs.