Methicillin-resistant Staphylococcus aureus (MRSA) causes more than 11,000 deaths in the United States each year and a new study shows how this pathogen is able to evade last-line antibiotics.
For today’s doctors, antibiotic-resistance superbugs can seem like elusive criminals evading capture. In further proof of just how wily these pathogens can be, a team of researchers has discovered that Methicillin-resistant Staphylococcus aureus (MRSA) bacteria release decoys to dodge the antibiotics administered to eradicate them.
MRSA makes the Centers for Disease Control and Prevention’s (CDC) top “Biggest Threats” list of 18 drug-resistant bacteria for good reason. In the United States, there are about 80,000 severe MRSA infections each year leading to more than 11,000 deaths. It’s one of the pathogens leading to far too many healthcare-associated infections, which patients can pick up in hospitals and other care facilities while receiving treatment for other conditions or undergoing surgery. Bacteria that come in contact with surgical wounds, urinary catheter lines, central lines for blood draws, and ventilators can lead to infection in hospital patients, particularly those who’ve received antibiotics that have wiped out their “good bacteria,” thus making it easier for pathogens to grow and take over.
A recent press release issued by the Imperial College London details recent findings on just how some resistant strains of MRSA are able to elude antibiotic treatment. The study was conducted by researchers at the college and the Medical Research Council’s Centre for Molecular Bacteriology and Infection, and published in the journal Nature Microbiology. Researchers examined how resistance leads to treatment failure in more than 20% of MRSA cases, even with the use of the last-resort drug daptomycin, and found that certain mutant forms of MRSA are able to survive exposure to the antibiotic by releasing membrane phospholipids, which effectively act as decoys and inactivate the drug.
“Antibiotics work by targeting vital machinery in bacteria,” study author Andrew Edwards, MB, BS, said in an interview with Contagion. “This kills the bacteria, or at least stops them from growing. However, in this work, we found that MRSA can release decoys that trick the antibiotic and divert the drug away from the bacteria.”
Dr. Edwards and his team found that while a wild-type S. aureus that released the decoys was quickly killed by daptomycin, a mutant version often found in clinical isolates also releases cytolytic toxins that results in treatment failure. When the researchers studied how the daptomycin worked on MRSA in mice, they found that the antibiotic decreased the wild-type bacteria 15-fold but did not create a significant decrease in the number of mutant bacteria. The authors also noted that staphylococcal infections are often caused by a mix of these MRSA strains, and that the presence of the mutant bacteria can help protect wild-type bacteria from the effects of daptomycin.
To try and improve treatment against these pathogens, the researchers tried a combination therapy with the beta-lactam antibiotic oxacillin, known to promote the activity of daptomycin. They found that at certain concentrations, oxacillin boosted daptomycin’s ability to kill the mutant S. aureus. The researchers also found that two antibiotics did not work as well together against wild-type S. aureus alone, but the combination was effective in mixed populations of the strains. “Most of our current drugs are safe, cheap and, for the most part, effective,” explains Dr. Edwards. “Therefore, we need to use our drugs in better ways to reduce the emergence of resistance.
Combination therapy is one potential way of doing this. However, whilst some combinations are synergistic, others can be antagonistic. Therefore, it’s essential to figure out which combinations are useful in treating each of the different types of infection that occur. We also need better diagnostics so that the best drug can be used as quickly as possible.”
The Imperial College London press release notes that a next generation antibiotic currently in clinical trials has been found to stop the production of decoys that have helped make MRSA so hard to treat. “Bacteria will evolve resistance to all of our effective antibiotics eventually,” says Dr. Edwards. “We need to use our current drugs better, to preserve their effective lifespan, and we need to develop new therapeutics. These might be new antibiotics or alternatives such as drugs that reverse resistance and allow current antibiotics to work against resistant bacteria.”