Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist.
Spaulding CN, Klein RD, Ruer S, Kau AL, Schreiber HL, Cusumano ZT, Dodson KW, Pinkner JS, Fremont DH, Janetka JW, Remaut H, Gordon JI, Hultgren SJ
Nature. 06 2017. doi: 10.1038/nature22972
COMMENT: Uropathogenic _Escherichia coli_ (UPEC) are one of the responsible agents for urinary tract infections (UTIs). Annually around 150 million people are affected by UTI caused by UPEC and it has been described an increment in the prevalence of antibiotics-resistance UPEC.
UPEC strains can establish reservoirs in the gut and can be carried to the vagina and periurethral area in faeces being able to colonize urinary tract from there.
Pili proteins play an important role in the intestinal and urinary tract colonization. UPEC strains encode up to 16 distinct chaperone-usher pathway pili operons. Each pili type allows them to colonize different body locations. For example, it is known the FimH type 1 pilus allows the bacteria to colonize bladder via binding to the mannose present in the bladder cells.
The authors show in this article a mouse model where the F17-like and type 1 pili promote intestinal colonization. Mutants lacking the _fim_ and the _ucl_ (F17-like and type 1 pili operons respectively) operons reduced significantly the mouse intestinal colonization and mutants lacking both operons simultaneously showed an even larger decrease of colonization suggesting both operons play non redundant roles in the colonization. Among the _fim_ encoded genes the FimH protein seemed to play a key role in the intestinal colonization as the depletion of only FimH enconding gene mirrored the effect of the depletion of the whole _fim_ operon. It has also been proven in other mouse models the importance of the FimH protein in the bladder colonization.
The binding of FimH to eptithelial cells is inhibited by the use of D-mannose and M4284 (a high-affinity mannose analogue) so the authors suggest the use this inhibitory mannoside for FimH, in addition to standard treatment for UTI, to reduce UPEC gut reservoirs and thus reducing the rate of UTIs and recurrent UTIs