Search & Destroy: Mechanisms of anti-plasmid immunity

Antibiotic resistance is one of the most pressing health challenges of our time. The culprits often hide in tiny circular DNA fragments called plasmids, which can jump between bacteria and spread resistance genes like wildfire. But bacteria are not defenceless: they possess their own immune systems to detect and destroy these genetic intruders. One of the most intriguing of these systems is known as DdmDE, found in the bacterium Vibrio cholerae, the pathogen behind cholera outbreaks. How this microscopic defence mechanism distinguishes between self and enemy DNA, however, remains a mystery. This project aims to uncover how the DdmDE system recognizes and eliminates invading plasmids while leaving the bacteriums own DNA untouched. Understanding this self- versus-non-self discrimination is essential to grasp how bacteria protect themselves and control the spread of antibiotic resistance. To do so, researchers will combine biochemical experiments, cryo-electron microscopy, and live-cell fluorescence imaging to visualize DdmDE in action from its first contact with foreign DNA to the complete destruction of a plasmid inside a living cell. This integrated approach will reveal the molecular steps that activate DdmDE and allow it to selectively degrade plasmids. Beyond its biological importance, this project could open new avenues for biotechnology. Systems like DdmDE represent a largely untapped source of programmable DNA-cutting tools, potentially complementing or even improving on CRISPR technologies. By decoding how bacteria achieve such precise DNA targeting, this research will not only advance our understanding of microbial immunity but may also lay the groundwork for the next generation of genome-editing methods.

No additional funding sources recorded.