Eric Wright, a researcher from the University of Pittsburgh and co-author of a recent study, stated, “Vancomycin has been a dependable treatment for MRSA for many years because it’s uncommon for S. aureus to develop resistance to it. However, our study indicates that vancomycin might not always be effective against MRSA in the future.”
Researchers initially believed that VRSA (Vancomycin-Resistant Staphylococcus aureus) developed mutations when exposed to vancomycin. To investigate this, they sequenced the genomes of bacteria grown with and without exposure to vancomycin. They discovered that mutations occurred in a specific gene mainly in bacteria exposed to vancomycin, but these mutations didn’t happen in bacteria grown without it.
VRSA results from the transfer of the vanA operon genes from another vancomycin-resistant bacterium to S. aureus. Researchers isolated VRSA strains and grew four of them, each containing the vanA operon, both with and without vancomycin exposure.
The study highlights the importance of developing new antibiotics to fight possible vancomycin-resistant S. aureus in the future. However, a limitation of the study is that it did not examine how the VRSA strains, which evolved in the lab, would behave in a living organism.
Understanding MRSA’s Growing Resistance to Vancomycin
Staphylococcus aureus is one of the leading bacteria contributing to the growing problem of antibiotic resistance in the 21st century. One of its strains, methicillin-resistant Staphylococcus aureus (MRSA), caused over 100,000 deaths in 2019, but vancomycin has remained an effective treatment for MRSA for the past 40 years.
Is Vancomycin Losing Its Effectiveness?
Although MRSA rarely resists vancomycin, there have been only 16 reported cases in India where S. aureus became resistant. This usually happens because vancomycin-resistant S. aureus (VRSA) tends to grow slower and is less effective than regular bacteria. However, researchers have now found that S. aureus can adapt to vancomycin and reduce the fitness loss associated with resistance. This study, published in PLoS Pathogens on August 29, suggests that the effectiveness of vancomycin against MRSA might not last forever.
Eric Wright, a researcher from the University of Pittsburgh and co-author of the study, said, “Vancomycin has been a reliable treatment for MRSA for years, but our research indicates that this might not always be the case.”
How VRSA Adapts to Vancomycin
All VRSA cases occur when S. aureus acquires a set of genes called the vanA operon from another vancomycin-resistant bacterium during simultaneous infection. To study this, researchers isolated VRSA strains from clinical samples, and four of them carrying the vanA operon were grown both with and without vancomycin exposure.
First, they grew VRSA in different conditions (solid and liquid cultures) with vancomycin to observe how it adapted. They discovered that VRSA grew more slowly than MRSA, showing that becoming resistant to vancomycin came with a fitness cost. When the bacteria were moved to an environment without vancomycin, they quickly lost their resistance, becoming susceptible again.
Researchers then let the VRSA strains evolve in the lab for 50 generations and compared them to their original versions. They found that many of these evolved strains grew faster than the original ones, suggesting that VRSA could adapt and overcome its initial resistance cost if exposed to vancomycin for a longer time.
In a separate experiment, VRSA was grown without vancomycin for 50 generations. These strains did not show the same improvements in growth, meaning the adaptation was mainly triggered by the presence of the antibiotic.
Mutations Play a Role
Researchers suspected that VRSA developed additional mutations when exposed to vancomycin, helping it overcome resistance costs. To verify this, they sequenced the genomes of bacteria grown with and without vancomycin. They found mutations in a specific gene present only in bacteria exposed to vancomycin.
They then tested whether these mutations contributed to overcoming fitness costs by comparing mutated and non-mutated strains. The VRSA strains with mutations grew faster in the presence of vancomycin, while those without mutations grew more slowly.
Next, the team tested whether the strains could revert to being sensitive to vancomycin. After exposing them to vancomycin for 50 cycles and then growing them in a vancomycin-free environment for 10 cycles, they found that most of the mutated strains remained resistant even without the antibiotic.
Finally, they tested whether adapting to vancomycin affected the strains’ resistance to other antibiotics like linezolid and oxacillin. They found that the evolved strains had reduced or lost resistance to oxacillin, although they could potentially regain it through other pathways.
Implications for Future Treatments
The study suggests that developing new antibiotics and treatment strategies is essential to tackle future vancomycin-resistant S. aureus strains. However, one limitation is that researchers did not test how the evolved VRSA strains would survive in a living organism.
Dr. Laasya Samhita, an assistant professor at Ashoka University who studies antibiotic resistance, commented on the study, stating that it adds to the existing research on vancomycin resistance in S. aureus. She emphasized that resistance to vancomycin often comes with a fitness cost, which is usually lost when the antibiotic isn’t present. The key finding of this study is that prolonged exposure to vancomycin allows VRSA to adapt and compensate for these costs, making it more difficult to treat and allowing it to spread more easily.
Dr. Samhita also noted that this study looked at only one type of resistance mechanism and that there are other ways bacteria can become resistant to vancomycin. She pointed out that the study does not discuss how to prevent bacteria from overcoming these resistance costs. However, the research highlights the importance of stopping vancomycin treatment immediately if VRSA is detected in patient samples.
(Sneha Khedkar is a biologist who transitioned into freelance science journalism. snehakhedkar30@gmail.com)