Identification of f imS Regulator Motifs in K. pneumoniae and E. coli to Advance Antivirulence Treatment of Type 1 Pili

UroPathogenic Escherichia coli (UPEC) and Klebsiella pneumoniae are the two main causative agents of urinary tract infections. Furthermore, these uropathogens are rapidly developing multi-drug resistance. However, as type 1 pili (filamentlike proteins) are critical virulence factors within both species, antivirulence treatment targeting the pili-encoding fim operon is a potential alternative to antibiotics for treatment. We used MEGA XI Mass Alignment Sequencing and phylogenetic analysis to identify conserved nucleotide regions among strains within select clades of UPEC and K. pneumoniae. From a sample of fim operon regulators, we identified statistically significant protein-binding motifs among the conserved regions using the Multiple Em for Motif Elicitation (MEME) Tool. We found the binding domains for the following regulator proteins to be highly conserved in the fimS region of E. coli reference strains: CitT, CovR, GlnR, IHF, RofA, XylR, SigW, PucR, Fur, MetR, and OxyR. CTSR and Hpr were completely conserved in K. pneumoniae reference strains, and PhoP is highly conserved in both species. These proteins are potentially associated with the pathogenicity of UPEC and K. pneumoniae. Together, these results indicate that antivirulence treatment targeting these regulators can be advanced. Future studies could conduct an electrophoretic mobility shift assay for confirmation of regulators' binding regions and genetic analysis through motif deletion/mutation to determine the regulators' functions.