Pectic Oligosaccharides from Cranberry Prevent Quiescence and Persistence in the Uropathogenic Escherichia coli CFT073

Abstract

Urinary tract infections (UTIs) caused by Escherichia coli create a large burden on healthcare and frequently lead to recurrent infections. Part of the success of E. coli as an uropathogenic bacterium can be attributed to its ability to form quiescent intracellular reservoirs in bladder cells and its persistence after antibiotic treatment. Cranberry juice and related products have been used for the prevention of UTIs with varying degrees of success. In this study, a group of cranberry pectic oligosaccharides (cPOS) were found to both inhibit quiescence and reduce the population of persister cells formed by the uropathogenic strain, CFT073. This is the first report detailing constituents of cranberry with the ability to modulate these important physiological aspects of uropathogenic E. coli. Further studies investigating cranberry should be keen to include oligosaccharides as part of the ‘active’ cocktail of chemical compounds.

Oligosaccharides and Complex Carbohydrates: A New Paradigm for Cranberry Bioactivity

“…Comparisons of 2D NMR spectra indicated that the structural features of uG4 m3 were representative for the Cranf1b-cPOS unsaturated methyl poly-galacturonoate series. The authors [133] observed that the formation of the 4,5-unsaturated bond in the Cranf1b-cPOS oligomers may have been due to eliminative cleavage resulting from the specific types of enzymes used to commercially process cranberry materials, further supporting the need for additional research into cranberry pectin structures and the effects of processing (see Section 1.2). by HPLC to obtain two compounds and the fraction HDP-cPOS, composed of a series of unsaturated methyl polygalacturonoates with DP 3-8 and one or two free carboxylic acid groups.…”

“…The use of multiple fraction names to describe essentially the same material has already led to some confusion regarding which cranberry materials and subfractions can be appropriately compared for even the relatively few studies investigating cranberry oligosaccharides to date [25][26][27][28][29]72,[112][113][114][115][131][132][133]. Insufficient material descriptions are also a problem as a minimal standardized method for characterizing and describing oligosaccharide fractions has yet to be established (see Table. Original, author-assigned fraction names have been used when possible but some (italics) have been elaborated upon or added to by the current authors to facilitate discussion.…”

“…Cranberry pectins have yet to be thoroughly investigated for structural features or biological properties. Some general structural features and properties of cranberry pectins have, however, been reported [43][44][45]72,112,139] and one study has reported structures for pectic oligosaccharides associated with the cranberry oligosaccharide material (Cranf1b) investigated in previous studies [133].…”

“…Sun et al [133] observed that the xyloglucan-containing Cranf1b material (from CHEP) was able to induce bacterial colony formation when added to the surface of an agar plate containing quiescent E. coli CFT073. Bioassay-guided fractionation led to the identification of a Cranf1b subfraction, Cranf1b-cPOS, that retained this property.…”

“…In contrast to growth inhibitory effects, cranberry oligosaccharides may have growth promoting effects independent of the use of these compounds by bacteria as growth substrates. Sun et al [133] reported that cranberry pectic oligosaccharide fractions of CHEP were able to promote the in vitro growth of quiescent and persister phenotypes of E. coli CFT073 under different culture conditions. Low concentrations of cranberry pectic oligosaccharide fractions Cranf1b-cPOS, HDP-cPOS, uG3 m2 , and uG4 m3 (8, Figure 10) were able to induce bacterial growth when applied to glucose-deficient agar plates containing an overlay of non-growing (quiescent) E. coli [133].…”