d-mannose treatment neither affects uropathogenic Escherichia coli properties nor induces stable FimH modifications

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 theemergence of antibiotic resistant strains. The natural sugar d-mannose is considered as an alternativeto antibiotics due to its ability to mask the bacterial adhesin FimH, thereby preventing its binding tourothelial cells. Despite its extensive use, the possibility that d-mannose exerts “antibiotic-like” activityby 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-mannosewere analyzed by standard microbiological methods. FimH functionality was analyzed by yeastagglutination and human bladder cell adhesion assays. Our results indicate that high d-mannoseconcentrations have no effect on bacterial growth and do not interfere with the activity of differentantibiotics. d-mannose ranked as the least preferred carbon source to support bacterial metabolismand growth, in comparison with d-glucose, d-fructose, and l-arabinose. Since small glucose amountsare physiologically detectable in urine, we can conclude that the presence of d-mannose is irrelevantfor bacterial metabolism. Moreover, d-mannose removal after long-term exposure did not alterFimH’s capacity to bind to mannosylated proteins. Overall, our data indicate that d-mannose is agood alternative in the prevention and treatment of UPEC-related UTIs.