Natural Polyphenols for Prevention and Treatment of Urinary Tract Infections

Maisto, Maria; Iannuzzo, Fortuna; Novellino, Ettore; Schiano, Elisabetta; Piccolo, V.; Tenore, Gian Carlo

doi:10.3390/ijms24043277

Cited by 8 publications

(8 citation statements)

References 108 publications

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“…In this study, we probed the anti-invasion properties of four well-studied plantderived phenolics: caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate (EGCG). These phenolics are similar to many found in extracts from cranberry and a variety of other medicinal plants, and have been linked, at least tentatively, with protection against UTI (10,66,69,(71)(72)(73)(74)(75)(76). Results presented here show that select phenolics can inhibit host cell invasion by UPEC, as well as other invasive pathogens.…”

Section: Introductionsupporting

confidence: 73%

“…( A and B ) BECs or ( C-H ) FAK+/+ and FAK-/-MEFs were treated with FAK14 (10 μg/mL), CAPE (25 µg/mL), resveratrol (22.9 μg/mL), carrier (DMSO) alone, or left untreated, as indicated, for 1 h prior to and during a 2-h infection with UTI89. Monolayers were then washed and processed to determine total numbers of host cell-associated bacteria or incubated for an additional 2-h period with gentamicin to eradicate extracellular bacteria.…”

Section: Resultsmentioning

confidence: 99%

“…Briefly, 5637 or MEF cells were seeded into 24-well tissue culture plates and grown for about 24 h to near confluency. Where indicated, cell monolayers were treated with CAPE (100.7 μM; 25 µg/mL), resveratrol (100 µM; 22.9 μg/mL), EGCG (54.5 μM; 25 µg/mL), catechin (86.1 μM; 25 µg/mL), FAK14 (10 μg/mL; 35 μM), or DMSO (carrier, 0.1% final concentration) in complete media for 1 h prior to infection. Alternatively, host cells were treated with actinomycin D (5 µg/mL), cycloheximide (26 µM), or an equal volume of ethanol (diluent) for 30 min prior to infection.…”

Section: Methodsmentioning

confidence: 99%

“…Oral administration of anti-invasion phenolic compounds faces similar challenges, in addition to potential problems with absorption and modification by metabolic processes and microbes within the gut (53,69,(133)(134)(135). Furthermore, the intake of very high amounts of plant-derived phenolics might have detrimental effects, such as iron depletion, liver and kidney toxicity, and irritation of the gastrointestinal tract (10,12,(136)(137)(138). Despite these limitations, the work presented here highlights the potential therapeutic utility of plant-derived phenolic compounds as a means to inhibit host cell invasion by UPEC which, if optimized, could help disrupt cycles of rUTIs in some individuals.…”

Section: Camp-phosphodiesterases Which In Turn Interferes With Actin ...mentioning

confidence: 99%

“…Especially intriguing are reports that phenolic and polyphenolic compounds derived from cranberry (Vaccinium macrocarpon) and other botanical sources may help protect against urinary tract infections (UTI) in some individuals (8)(9)(10)(11)(12). These infections, which are most often caused by strains of uropathogenic Escherichia coli (UPEC), are exceptionally common and prone to recur (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Plant Phenolics Inhibit Focal Adhesion Kinase and Suppress Host Cell Invasion by UropathogenicEscherichia coli

Lewis,

Richards,

Mendez

et al. 2023

Preprint

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Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic and polyphenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here we tested a panel of four well-studied phenolic compounds – caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate – for effects on host cell adherence and invasion by uropathogenicEscherichia coli(UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses, and likely contribute to the development of chronic and recurrent infections. Using cell culture-based assays, we found that only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK, or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model, and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches.IMPORTANCEUrinary tract infections (UTIs) are exceptionally common and increasingly difficult to treat due to the ongoing rise and spread of antibiotic resistant pathogens. Furthermore, the primary cause of UTIs, uropathogenicEscherichia coli(UPEC), can avoid antibiotic exposure and many host defenses by invading the epithelial cells that line the bladder surface. Here we identified two plant-derived phenolic compounds that disrupt activation of the host machinery needed for UPEC entry into bladder cells. One of these compounds (resveratrol) effectively inhibited UPEC invasion of the bladder mucosa in a mouse UTI model, and both phenolic compounds significantly reduced host cell entry by other invasive pathogens. These findings suggest that select phenolic compounds can be used to supplement existing antibacterial therapeutics by denying uropathogens shelter within host cells and tissues, and help explain some of the benefits attributed to traditional plant-based medicines.

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