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 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.

FimH and Anti-Adhesive Therapeutics: A Disarming Strategy Against Uropathogens

“…In Europe, the AMR of uropathogens is deeply detailed by the surveillance system of the European Center of Diseases Prevention and Control (ECDC) ( ). To counteract AMR, several alternative therapeutic approaches are emerging, including anti-adhesive strategies [ 4 , 6 , 10 , 13 , 24 ]. Uropathogens belonging to the Enterobacteriaceae family share a huge number of virulence factors known to be involved in the adhesion, colonization and invasion of host tissues, offering the possibility to develop different and specifically targeted anti-adhesive strategies.…”

“…Urinary tract infections (UTIs) caused by different microbial agents, including both Gram-positive and Gram-negative bacteria and fungi, are among the most prevalent infectious diseases affecting millions of people annually [ 1 , 2 , 3 , 4 , 5 , 6 ]. Most UTIs are community- and nosocomial-acquired infections, which can occur in any part of the urinary tract [ 4 , 6 , 7 , 8 , 9 , 10 ]. Among the Gram-negative bacteria, the uropathogenic Escherichia coli (UPEC) accounts for 50% of nosocomial- and up to 95% of community-acquired UTIs, followed by the uropathogenic Klebsiella pneumoniae (UPKP) and the uropathogenic Proteus mirabilis (UPPM) [ 1 , 6 , 11 , 12 ].…”

“…Although UTIs can occur in both male and female patients, the number of female patients is significantly higher than male patients due to the anatomical features of women. These features include the shortness of the urethra, the urethral meatus’s proximity to the anus, and the more humid surrounding environment compared to the male anatomy [ 1 , 4 , 5 , 6 , 10 ]. Despite receiving appropriate antibiotic therapy, 20–30% of women who have already experienced an initial UTI develop a recurrent infection (rUTI) within 4–6 months.…”

CT and MRI in Urinary Tract Infections: A Spectrum of Different Imaging Findings

“…UTIs can be caused by many types of micro-organisms, including Gram-positive bacteria, Gram-negative bacteria and certain fungi. Uropathogenic Escherichia coli (UPEC) is the commonest causative organism for both complicated and uncomplicated UTIs [ 5 , 6 , 7 , 8 ]. Undetected and untreated acute pyelonephritis may lead to renal hypertension, renal scarring, and even renal failure [ 9 ].…”

A Novel Pseudomonas geniculata AGE Family Epimerase/Isomerase and Its Application in d-Mannose Synthesis

“…It does not cause significant increases in blood sugar because it cannot be well metabolized in the body, and it has been extensively employed in the food, pharmaceutical, and feed industries [2,3]. Recently, researchers described the application of d-mannose as a good alternative in the prevention and treatment of urinary tract infections (UTIs) [4,5]. d-mannose can be extracted from jujube, apple pulp, and orange peel [6][7][8].…”