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.
Highlights
Urinary tract infections (UTIs) are among the most common infectious diseases, affecting more than 150 million people worldwide each year [1,2]
To evaluate whether D-mannose might affect bacterial growth, strain CFT073 was streaked on Hinton agar (MHA) plates supplemented with diverse sugars at different concentrations
To evaluate whether d-mannose might affect bacterial growth, strain CFT073 was streaked on the range of D-mannose dosage for UTI prevention used in clinical trials was between 2 and 3 g per Mueller Hinton agar (MHA) plates supplemented with diverse sugars at different concentrations day and that the normal urine volume is 800 to 2000 mL/day, it is reasonable to speculate that D(d-mannose, d-glucose, d-fructose, and l-arabinose)
Summary
Urinary tract infections (UTIs) are among the most common infectious diseases, affecting more than 150 million people worldwide each year [1,2]. The increase in antibiotic resistance found in clinical UPEC isolates has made UTI management progressively costlier and more challenging [5,10,18] On this basis, several promising efforts have been made to study novel strategies aimed at counteracting bacterial virulence factors without affecting bacterial lifestyle, metabolism, or multiplication. While validated in only three clinical trials studies, d-mannose, administered at high dosage, revealed its efficacy both in reducing the symptoms and the recurrence rate of UTIs [31,34,36] Despite these promising results, the possibility that d-mannose exerts only anti-adhesive activity on FimH without altering bacterial growth and/or metabolism not have been addressed yet.
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