Antiphage Systems Leave Bacteria Prone to Antibiotics

In a recent scientific publication, researchers from the Universities of Tübingen and Würzburg have uncovered an interesting interplay between the bacterial immune system and an antifolate class of antibiotics. The unlikely partners in this microbial drama? Vibrio cholerae, the culprit behind severe cholera outbreaks, and antifolate antibiotics, one of the oldest players in the antibiotic game.

Picture this: Bacteria, armed with a sophisticated immune system wield it against viral invaders called bacteriophages. But in an unexpected turn of events, this defence mechanism has been found not just warding off viruses but also cranking up the potency of antifolate antibiotics against Vibrio cholerae. The revelation, laid bare in the latest publication of Nature Microbiology, has researchers buzzing with excitement.

Vibrio cholerae, a notorious troublemaker on the global health stage, deploys a defense system that includes a mouthful of an acronym—CBASS, or cyclic-oligonucleotide-based antiphage signalling system. Traditionally activated during bacteriophage onslaughts, CBASS triggers a self-destruct sequence in the infected bacterium, putting a stop to further infections in its microbial neighbourhood.

Now, imagine this immune system getting a little trigger-happy, not just during viral attacks but even in the absence of the usual suspects, the bacteriophages. Why? Because, as the researchers found, antifolate antibiotics have a secret handshake with CBASS. They discovered that these antibiotics, known for disrupting the synthesis of DNA-building folates, manage to activate CBASS, turning the bacterium's own immune response against itself. It's like a double-edged sword where the bacteria are inadvertently damaged by their own defenses.

Antifolates, the old-timers of the antibiotic world with a history spanning over 90 years, were thought to have revealed all their secrets. But no—this study suggests there is more to learn about their modus operandi. Some studies have suggested how resistance shifts between antibiotics and antiphage systems in bacteria occur, highlighting that bacteria have to lose one to build another.

Structures of classical antifolates | Antiphage System Leaving Bacteria Prone to Antibiotics
Structures of classical antifolates Credit Mitchell Ryan et al 2013

So, what's the takeaway from this microbial saga? According to the study, understanding how antibiotics dance with the bacterial immune system gives us a strategic advantage. It's not just about choosing which antibiotics to use; it's about deciding whether to go solo, form a combo, or even partner up with phage therapy. In a world where antibiotic resistance is an ever-growing concern, this newfound knowledge could be the game-changer we've been waiting for. The battleground may be microscopic, but the implications are monumental. Stay tuned for the next twist in the microbial saga, as science unravels the secrets of bacterial warfare.

Read this full article here Susanne Brenzinger et al, The Vibrio cholerae CBASS phage defence system modulates resistance and killing by antifolate antibiotics, Nature Microbiology (2024). DOI: 10.1038/s41564-023-01556-y

About the author

Hello there!

I'm Raphael Hans Lwesya. I have a deep interest in phage research and science communication. I strive to simplify complex ideas and present the latest phage-related research in an easy-to-digest format. Thank you for visiting The Phage blog. If you have any questions or suggestions, please feel free to leave a comment or contact me at [email protected].


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