Ricerc@Sapienza

Abstract: Urinary tract infections (UTIs) are mainly caused by uropathogenic Escherichia coli (UPEC).
Acute and recurrent UTIs are commonly treated with antibiotics, the efficacy of which is limited by the
emergence of antibiotic resistant strains. The natural sugar d-mannose is considered as an alternative
to antibiotics due to its ability to mask the bacterial adhesin FimH, thereby preventing its binding to
urothelial cells. Despite its extensive use, the possibility that d-mannose exerts “antibiotic-like” activity
by altering bacterial growth and metabolism or selecting FimH variants has not been investigated yet.
To this aim, main bacterial features of the prototype UPEC strain CFT073 treated with d-mannose
were analyzed by standard microbiological methods. FimH functionality was analyzed by yeast
agglutination and human bladder cell adhesion assays. Our results indicate that high d-mannose
concentrations have no effect on bacterial growth and do not interfere with the activity of different
antibiotics. d-mannose ranked as the least preferred carbon source to support bacterial metabolism
and growth, in comparison with d-glucose, d-fructose, and l-arabinose. Since small glucose amounts
are physiologically detectable in urine, we can conclude that the presence of d-mannose is irrelevant
for bacterial metabolism. Moreover, d-mannose removal after long-term exposure did not alter
FimH’s capacity to bind to mannosylated proteins. Overall, our data indicate that d-mannose is a
good alternative in the prevention and treatment of UPEC-related UTIs.