E. coli and your receptors

Ok. This is cool. I took a break from grant-writing to read this paper, and I’m glad that I did. Starting with an in silico screen, Cirl et al. showed that some pathogenic bacteria (they focused on uropathogenic E. coli) secrete proteins that are homologues of a domain of the mammalian toll-like receptors (TLR). TLR are the sentinel molecules of the innate immune system, detecting conserved pieces of pathogens (peptidoglycan, lipopolysaccharide, or good-old bacterial DNA) and initiating immune responses. They are present on all kinds of cells, including the epithelial cells that line the urinary tract. The E. coli proteins that this group found bind to the TIR domain, the part of TLR that are responsible for transducing signals, and interrupt the signaling cascade, effectively silencing the alarm. This blunts the immune response and, presumably, protects the bacteria from attack. The paper is a great piece of work, telling a coherent story and taking the idea from the initial screen to a mechanistic investigation that has real clinical implications. Well done!

Link to article. (Sadly, not open access.)


Cirl, C., Wieser, A., Yadav, M., Duerr, S., Schubert, S., Fischer, H., Stappert, D., Wantia, N., Rodriguez, N., Wagner, H., Svanborg, C., Miethke, T. (2008). Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain–containing proteins. Nature Medicine DOI: 10.1038/nm1734