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Adaptive mutations in the signal peptide of the type 1 fimbrial adhesin of uropathogenic Escherichia coli

Ronald, Leah S., Yakovenko, Olga, Yazvenko, Nina, Chattopadhyay, Sujay, Aprikian, Pavel, Thomas, Wendy E., Sokurenko, Evgeni V.
Proceedings of the National Academy of Sciences of the United States of America 2008 v.105 no.31 pp. 10937-10942
adhesins, bacteria, bacterial adhesion, bladder, cell membranes, epithelial cells, fimbriae, humans, mutants, mutation, neutrophils, organelles, signal peptide, uropathogenic Escherichia coli
Signal peptides (SPs) are critical for protein transport across cellular membranes, have a highly conserved structure, and are cleaved from the mature protein upon translocation. Here, we report that naturally occurring mutations in the SP of the adhesive, tip-associated subunit of type 1 fimbriae (FimH) are positively selected in uropathogenic Escherichia coli. On the one hand, these mutations have a detrimental effect, with reduced FimH transport across the inner membrane, fewer FimH and fimbriae expressed on the bacterial surface, and decreased bacterial adhesion under flow conditions. On the other hand, the fimbriae expressed by the mutants are significantly longer on average, with many fimbriae able to stretch to >20 μm in length. More surprisingly, the SP mutant bacteria display an increased ability to resist detachment from the surface upon a switch from high to low flow. This functional effect of longer fimbriae highlights the importance of the nonadhesive fimbrial rod for adhesive function. Also, whereas bacterial adhesion to bladder epithelial cells was preserved in most mutants, binding to and killing by human neutrophils was decreased, providing an additional reason the SP mutations are relatively common among uropathogenic strains. Thus, this study demonstrates how mutations in an SP, while decreasing transport function and not affecting the final structure of the translocated protein, can lead to functional gains of the extracellular organelles that incorporate the protein and overall adaptive changes in the organism's fitness.