Jekyll and Hyde; when good bacteria turn bad

Identifying key molecular triggers that transform bacteria from “good to bad” is critical to understand and control inter-conversion between beneficial and harmful properties. Our research has found two phylogenetically similar strains of Lactobacillus fermentum which have contrasting effects on intestinal epithelial barrier integrity. One strain, AGR1485, was found to maintain the barrier integrity of cultured human epithelial colorectal adenocarcinoma Caco-2 cell monolayers, while the other, AGR1487, decreased the integrity. A healthy intestinal barrier is essential to preventing unwanted components entering our body and causing inflammatory and autoimmune diseases.
We are seeking an outstanding PhD candidate to undertake research to determine the genetic mechanisms responsible for the different effects of the two L. fermentum strains. Initial comparative analyses of draft genome sequences reveal that the strains have highly similar gene contents. However, a small number of loci have been found in AGR1487 but not AGR1485. These strains provides a unique opportunity to understand how the difference of a few factors may impact the health of the host, and how its manipulation can radically alter the balance of host microbial interactions. Using comparative genomics analyses, RNA sequencing, and site directed mutagenesis, the student will elucidate mechanisms that determine how phylogenetically similar strains can have markedly different effects and further the knowledge of Lactobacillus genome biology and its interactions with the health of the host.