How Mycobacterium abscessus Gains Resistance to Phage Therapy and How to Prevent It

What is it about?

Mycobacterium abscessus is a challenging bacterium to treat because many antibiotics are ineffective against it. Phage therapy uses viruses (phages) that naturally infect bacteria, and it has shown promise for treating some difficult infections. Most studies on phages against M. abscessus have focused on the “rough” form of the bacterium. However, many infections observed in parts of Asia are caused by the “smooth” form. In our study, we tested phages that can attack smooth bacteria and investigated how the bacteria respond under phage pressure. We found that some smooth bacteria can switch to a rough form, which helps them escape phage infection. We then showed that using a layered phage combination, one phage for smooth bacteria and another that can hit the rough escape variants, can reduce resistance and enhance treatment effectiveness

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Photo by CDC on Unsplash

Photo by CDC on Unsplash

Why is it important?

This work highlights an important limitation of phage therapy: bacteria can evolve quickly, and escape routes may also create forms that are difficult to treat and potentially more harmful. By identifying a specific resistance pathway (smooth-to-rough switching linked to surface glycolipid changes) and demonstrating a practical way to counter it, our findings provide a clear design principle for building more durable phage cocktails. It also expands knowledge of phage therapy to better address smooth M. abscessus infections, which are understudied but clinically common in Asia.

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