Role of FimK in Mediating Host Urinary Bladder Epithelial Cell Association of Uropathogenic Klebsiella Pneumoniae and Quasipneumoniae

Klebsiella spp. commonly cause both uncomplicated urinary tract infection (UTI) and recurrent UTI (rUTI). K. quasipneumoniae, a relatively newly defined species of Klebsiella, has been shown to be metabolically distinct from K. pneumoniae, but its urovirulence mechanisms have not been defined. Type 1 and type 3 fimbriae, encoded by fim and mrk operons respectively, mediate attachment of Klebsiella spp. to host epithelial cells. fimK is a regulatory gene unique to the Klebsiella fim operon that encodes an N-terminal DNA binding domain and a C-terminal phosphodiesterase domain that has been hypothesized to cross-regulate type 3 fimbriae via modulation of cellular levels of cyclic di-GMP. Comparative genomic analysis between K. pneumoniae and K. quasipneumoniae revealed a conserved premature stop codon in K. quasipneumoniae fimK that results in loss of the C-terminal phosphodiesterase domain (PDE). We hypothesized that this truncation would ablate cross-regulation of type 3 fimbriae in K. quasipneumoniae. Here, we report that K. quasipneumoniae KqPF9 bladder epithelial cell association and invasion is dependent on type 3 but not type 1 fimbriae. Further, we show that basal expression of both type 1 and type 3 fimbrial operons as well as bladder epithelial cell association are higher in KqPF9 than in K. pneumoniae TOP52. Interestingly, complementation of KqPF9∆fimK with the TOP52 fimK allele markedly reduced type 3 fimbrial expression and bladder epithelial cell attachment, a phenotype that was rescued by mutation of the C-terminal PDE active site. Taken together these data suggest that C-terminal PDE of FimK modulates type 3 fimbrial expression in K. pneumoniae and its absence in K. quasipneumoniae leads to a loss of type 3 fimbrial cross-regulation.