Antimicrobial resistance is one of the top 10 global threats to public health, according to the World Health Organization, and scientists are scrambling to find new tools to treat the deadliest drug-resistant infections. However, this study suggests that reducing the virulence of persistent infections rather than trying to kill the bacteria may offer an alternative treatment approach.

The study, published February 13, 2023, in the journal Proceedings of the National Academy of Science, suggests that therapy targeting these two proteins could disable MRSA, making it less deadly and possibly even harmless. Such an approach would also reduce the risk of developing antibiotic resistance.

We were looking for an alternative way to fight MRSA. We were interested in understanding how bacteria cause disease to see if we could directly interfere with the virulence factors produced by the bacteria. If we can neutralize him, maybe we don’t have to worry about his immunity to antimicrobials.

Why have bacteria become resistant to drugs?

Antimicrobial resistance develops when drug therapy kills some, but not all, bacterial cells. The remaining bacteria have some natural resistance, so if they have a chance to colonize again, the next infection will be stronger against antibiotics. This unintentional selective breeding has led to the emergence of superbugs such as MRSA and multidrug resistant tuberculosis.

A treatment approach that makes an infection less harmful without killing it could eliminate the possibility of such selective selection. In the case of MRSA, this is hindered by the fact that the bacterium produces several types of toxins in large quantities. Understanding and shutting down every mechanism is extremely difficult.

What scientists have learned

Previous work by Dickey and other researchers has shown that the two proteins act as ferries to transport toxin molecules from the bacterial cell membrane to the external environment. But it wasn’t clear why there were two carrier proteins and how they worked. Without this understanding, scientists cannot develop treatments that will prevent the release of toxins.

To understand the mechanism, Dickey and his team removed all types of carriers through genetic engineering and watched how MRSA cells secreted toxins. They discovered that a carrier protein collects hydrophilic or water-loving toxins floating in the cell’s cytoplasm and transports them across the cell membrane. In the absence of this carrier, hydrophilic toxins continued to accumulate inside MRSA cells, where they were harmless to both MRSA and any potential host.

When the team deleted the second carrier protein, hydrophobic (water-repellent) toxins accumulated in the cell. This is important because these toxins tend to leave the aqueous cytoplasm on their own and settle into the more oily cell membrane. This is where MRSA toxins damage host cells and MRSA cells. Therefore, without a second carrier protein, MRSA cells are damaged by their own hydrophobic toxins.

Why is this a really important discovery?

The study’s findings aren’t just for MRSA. When the researchers analyzed the genomes of many other bacteria, they found that many of them had genes that produce a dual system of transport proteins similar to what they found in MRSA. This discovery points to the potential of a new approach to treat other bacterial infections.

Overall, this study provides new insights into the complex mechanisms of bacterial virulence and offers hope for new approaches to combat drug-resistant infections.