Evolution of bacterial pathogens

Bacterial pan-genomes

Bacteria can take up short pieces of foreign DNA and integrate them into their genome. Those pieces mostly come from close relatives, but can also derive from more distantly related species or be shuttled by viruses. Via such horizontal mechanisms of inheritance, bacteria can acquire new proteins that help the bacterium to adapt to new environments, for example by providing enzymes that can digest a new food source or resistance factors that help to break down antibiotics. The union of all genes in genomes of a group or related bacteria is called the pan-genome. This pan-genome is often many times larger than the genomes of individual strains.

The mix of vertical inheritance, horizontal transfer, gene loss, and duplications generate a complex web of relationships between bacterial genomes, that is difficult to analyze. Wei Ding developed panX, a web-based application, to visualize the bacterial pan-genomes and provide tools for interactive exploration. PanX is designed to help spotting relevant patterns of bacterial evolution and ecology.

panX implements an interactive browser for bacterial pan-genomes. For each orthologous gene cluster, the browser displays the alignment, the gene tree, and the patterns of presence and absence of the gene among strains. All genes in the pan-genome are included in a table that is searchable for annotation or gene names.
Meta-information such as sampling location, habitat, etc.~can be overlayed with the trees to spot associations.
The visualization is coupled to a fast and accurate pan-genome identification pipeline but can also use the output of the popular pan-genome software roary.

panX is available at pangenome.de, an animated overview of its different components is shown here:

overall2

Drug resistance evolution of bacteria

Erdal Troprak (now at Southwestern University, at the time in the group of Roy Kishony) developed a continuous culture device call morbidostat that adjusts the antibiotic concentration in bacterial cultures to always slightly sublethal levels and maintains selective pressure for increased drug resistance. We built such a device and study colistin resistance evolution in Pseudomonas aeruginosa. This project was spear-headed by Bianca Regenbogen (now at U. Hohenheim) in collaboration with Silke Peter and Matthias Willmann from the Tuebingen medical school.