Evolutionary fine-tuning of conformational ensembles in FimH during host-pathogen interactions
Sciences Advances, e1601944 (2017)
Kalas, V., Pinkner, J.S., Hannan, T.J., Hibbing, M.E., Dodson, K.W., Holehouse, A.S., Zhang, H., Tolia, N.H., Gross, M.L., Pappu, R.V., Janetka, J., Hultgren, S.J.
This paper is a true tour-de-force of work from first author Vasilios, who combined multiple crystal structures, solution small angle X-ray scattering, time-of-flight mass-spec, all atom simulations, and even mouse models to build a comprehensive description of how single mutations in a bacterial cell adhesion protein influence the evolutionary landscape of E. coli in a bi-directional way.
Mutations in the two-domain type 1 pilus adhesin FimH can change the ability of uropathogenic E. coli to bind to the bladder wall, a process necessary for colonization, which in turn is responsible for ~85% of urinary tract infections. Naively, one might expect a direct correlation between binding affinity and infectivity, but as it turns out, there is a balance between high affinity binding that will alert the immune system (triggering an immunogenic response) and lower affinity binding that allows the bacteria to remain in “stealth mode”. The work demonstrates an example of selection for specific biophysical traits that are only advantageous due to a coupled evolutionary process associated with the host (in this case, the immune system), providing a direct demonstration of habitat-specific evolution.