Bacteria have demonstrated an unexpected evolvability that jeopardizes our efforts to control infections with antibiotics. An important element used by bacteria to evolve and adapt to clinical settings are integrons, a unique type of genetic platform that provides the bacterial host with novel functions through the recruitment of new genes encoded in cassettes. These elements play a major role in multidrug resistance in clinically relevant bacteria, since they are often found on plasmids, carrying a cargo of cassettes devoted to produce resistance to multiple antibiotics. But integrons are also found in the chromosomes of environmental bacteria harboring long arrays of cassettes of unknown function.

In this project we want to understand the adaptive value of integrons in both environments. Yet the study of chromosomal integrons has been blocked since their discovery, because the native integron will interfere with our tools to study it, biasing our results. To overcome these limitations we propose to delete the Superintegron, a massive structure encoded in the chromosome of Vibrio cholerae, the bacteria that causes Cholera.

 

 

Vibrio cholerae's Superintegron

 

 

We propose a novel approach to delete the structure and obtain a bacterial strain in which studies can be delivered. We will then use it to start answering major questions that have been out of reach. We will investigate the functions encoded in chromosomal integrons of environmental bacteria, including those of pathogenic Vibrio. We will deliver a method to unveil the genetic basis of how cassettes are created; and we will study the ecology of resistance genes in all fields of the One Health concept through the design of a biotechnological tool that captures cassettes from DNA samples. Understanding the origin and function of cassettes, and the circulation of resistance genes in cassettes will unveil important aspects of a genetic element that represents today a major threat to modern medicine.