The two principal investigators in this collaboration propose to study the evolution of a bacterium from a commensal to a pathogen through selection operating on pre-existing alleles, rather than through the acquisition of substantially different genes through horizontal transfer. (An example of the latter phenomenon is the """"""""pathogenicity island"""""""" or a bacteriophage with a toxin gene.) The investigators use the term """"""""pathoadaption"""""""" for the process of selection of allele variants that """"""""promote adaptation of the bacterial pathogens to a particular mode of pathogenesis."""""""" They propose to use for a model system type 1 fimbriae and adhesins of Escherichia coli and in particular the evolution of the adhesins for adaptation to the urinary tract and upper respiratory tract. For the study, the investigators will gather together representative strains and further characterize the fimbrial genes and the control regions for the genes. They will use Single Stranded Conformational Polymorphism and sequencing to distinguish the variants and to identify """"""""signatures"""""""" for adaptation to the human host microenvironment in a survey type of study. In a prospective study they will use an animal model to test their hypothesis that variant alleles of fimbrial genes that promote persistence in the animal urinary tract will be selected and then detected in the population.
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