This work seeks to generate new knowledge about the mechanisms underlying the protective effects of cranberry against urinary tract infections (UTI). Using Caco-2 cells grown in Transwell inserts as an intestinal barrier model, we found that a cranberry-derived digestive fluid (containing 135 ± 5 mg of phenolic compounds/L) increased transepithelial electrical resistance with respect to control (ΔTEER = 54.5 Ω cm2) and decreased FITC-dextran paracellular transport by about 30%, which was related to the upregulation of the gene expression of tight junction (TJ) proteins (i.e., occludin, zonula occludens-1 [ZO-1], and claudin-2) (∼3-4-fold change with respect to control for claudin-2 and ∼2-3-fold for occludin and ZO-1). Similar protective effects, albeit to a lesser extent, were observed when Caco-2 cells were previously infected with uropathogenic Escherichia coli (UPEC). In a urinary barrier model comprising T24 cells grown in Transwell inserts and either noninfected or UPEC-infected, treatments with the cranberry-derived phenolic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and phenylacetic acid (PAA) (250 μM) also promoted favorable changes in barrier integrity and permeability. In this line, incubation of noninfected T24 cells with these metabolites induced positive regulatory effects on claudin-2 and ZO-1 expression (∼3.5- and ∼2-fold change with respect to control for DOPAC and ∼1.5- and >2-fold change with respect to control for PAA, respectively). Overall, these results suggest that the protective action of cranberry polyphenols against UTI might involve molecular mechanisms related to the integrity and functionality of the urothelium and intestinal epithelium.

UNASSIGNED: Antibiotic resistance presents a significant global public health challenge, particularly for urinary tract infections (UTIs), and is notably severe in developing countries. Surveillance of the antimicrobial susceptibility patterns of UTI-causing bacteria is crucial for effective treatment selection. This study aimed to analyze these patterns in bacteria isolated from the urine samples of patients at Mughda Medical College Hospital, Dhaka, Bangladesh.
UNASSIGNED: A retrospective study (January 2019 to December 2020) at Mugdha Medical College and Hospital, Dhaka, examined clinical and laboratory data from patients with positive urine cultures (≥105 CFU/mL). The study classified patients into four age groups: children (1-<18 years), young adults (18-<33 years), middle-aged adults (33-50 years), and old adults (>50 years). The standard Kirby-Bauer method was used to assess antibiotic sensitivity to 28 common antibiotics.
UNASSIGNED: Among 243 positive urine cultures in both community- and hospital-acquired UTIs, Escherichia coli was the most common uropathogen (65.84%), followed by Klebsiella spp. (12.34%), Enterococcus spp. (8.23%), and other types of bacteria.
UNASSIGNED: Old adults are particularly vulnerable to UTIs, with E. coli being the predominant causative agent in the study region. The observed antimicrobial resistance patterns underscore the necessity of judicious antibiotic selection to effectively treat UTIs across different age groups.

Glycoproteins, in which polysaccharides are usually attached to proteins, are an important class of biomolecules that are widely used as therapeutic agents in clinical treatments for decades. Uropathogenic Escherichia coli (UPEC) O21 has been identified as a serogroup that induces urinary tract infections, with a global increasing number among women and young children. Therefore, there is an urgent need to establish protective vaccines against UPEC infection. Herein, we engineered non-pathogenic E. coli MG1655 to achieve robust, cost-effective de novo biosynthesis of O21 O-antigen polysaccharide-based glycoprotein against UPEC O21. Specifically, this glycoengineered E. coli MG1655 was manipulated for high-efficient glucose-glycerol co-utilization and for the gene cluster installation and O-glycosylation machinery assembly. The key pathways of UDP-sugar precursors were also strengthened to enforce more carbon flux towards the glycosyl donors, which enhanced the glycoprotein titer by 5.6-fold. Further optimization of culture conditions yielded glycoproteins of up to 35.34 mg/L. Glycopeptide MS confirmed the preciset biosynthesis of glycoprotein. This glycoprotein elicited antigen-specific IgG immune responses and significantly reduced kidney and bladder colonization. This bacterial cell-based glyco-platform and optimized strategies can provide a guideline for the biosynthesis of other value-added glycoproteins.

Background: Urinary tract infections (UTIs) are a prevalent form of urinary tract diseases affecting individuals of all ages and genders. In the Kingdom of Saudi Arabia (KSA), UTIs are a significant burden on the healthcare system, comprising 10% of all infections and ranking as the second leading cause of emergency department admissions. Despite this, limited research has been conducted in Saudi Arabia, particularly in Jazan Province, located in the southwestern region. Methods: This retrospective, cross-sectional study encompassed individuals with positive urine cultures who sought care at a tertiary hospital in Jazan between January 2022 and March 2023. A standardized data collection form was utilized to retrieve relevant information from microbiology lab test results and patients\' electronic medical records. Variables such as sex, urine sample collection date, bacterial isolates, antibiotic sensitivity, and resistance were collected using the data collection form. Data were analyzed using SPSS software, version 23.0 (IBM Corp., Armonk, NY, USA). Results: A total of 1082 urinary bacterial samples were isolated and identified. Females accounted for more bacterial infections (62.66%) than males (37.34%). Gram-negative bacteria represented 94% of all isolated strains. The most prevalent pathogens associated with UTIs were Escherichia coli (47.97%), Klebsiella pneumoniae (24.58%), and Pseudomonas aeruginosa (11.55%). Antimicrobial resistance patterns indicated the presence of extended-spectrum beta-lactamase (ESBL) (30.13%), carbapenemase-resistant Enterobacter (CRE) (1.94%), methicillin-resistant Staphylococcus aureus (MRSA) (0.74%), and vancomycin-resistant Enterococci (VRE) (0.18%). UTI incidence demonstrated a higher prevalence in September (13%) compared to other months in 2022. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the predominant Gram-negative multidrug-resistant organisms (MDRO), accounting for 34.42%, 13.95%, and 1.63% of the population. Conclusions: The prevalence of UTIs caused by antibiotic-resistant microbes is notable in Jazan. Consistent with findings from other regions, Escherichia coli remains the most common causative pathogen of UTIs, displaying a seasonal pattern that warrants attention. Approximately 35% of reported cases involve MDRO, with ESBLs accounting for 30%. These results should raise concerns among healthcare officials, highlighting the necessity for further investigations into factors contributing to the circulation of MDRO in Jazan.

Background: The present study evaluates the efficacy of bacteriophage therapy for urinary tract infection (UTI) in rats. Methods: UTI was established by inoculating Escherichia coli (100 μl) at a concentration of 1.5 × 108 CFU/ml per urethra via a cannula in different groups of rats. For treatment, phage cocktails (200 μl) were administered at varying concentrations of 1 × 108 PFU/ml, 1 × 107 PFU/ml and 1 × 106 PFU/ml. Results: The two doses of phage cocktail at the first two concentrations resulted in the cure of UTI. However, the lowest concentration of the phage cocktail warranted more doses to eradicate the causative bacteria. Conclusion: The quantity, frequency and safety of doses could be optimized in a rodent model using the urethral route.
Antimicrobial resistance is primarily caused by antibiotic overuse and misuse, which results in a decline in the ability of antibiotics to treat infections. Urinary tract infections (UTIs) are common but difficult to treat, as they are frequently caused by multidrug-resistant bacteria. Escherichia coli is a common cause of UTIs. Bacteriophages are a potentially viable alternative for the treatment of bacterial infections, and despite the numerous benefits of using phages as antibacterial therapeutics, there are surprisingly few original research articles based on clinical trials, specifically against UTIs. In this study, the efficiency of a customized bacteriophage cocktail for the treatment of UTIs, with varied doses administered directly into the urinary bladder of rats, was evaluated. At higher concentrations, UTIs were completely eradicated after two doses of the bacteriophage cocktail. However, at lower concentrations, additional doses were required to eradicate the infection. Phage therapy appears to have therapeutic potential, and this study indicates the potential frequency of dosages at appropriate concentrations. Phage therapy was both effective and safe.

Urinary tract infections (UTI) are frequent bacterial infections in childhood. Considering the known beneficial effects of probiotics in the gastrointestinal field, they could also help to alleviate UTIs. In our clinical pilot study, we sought to verify the positive effects of the specific probiotic strain on the course and prevention of UTI in children. Thirty children with UTIs were enrolled and sequentially sampled into two groups (placebo/control and probiotic/test) in a double-blind, randomized, placebo-controlled clinical pilot study. We chose Lactobacillus plantarum PCS 26 (Lp26) derived from local Slovenian cheese in Pathogen Combat Project, which showed a good in vitro antimicrobial effect on Escherichia coli (E. coli). Several parameters were followed to look for differences between both groups in the acute phase of the UTI and after 6 months of taking probiotic or placebo supplementation. Our results showed no statistically significant differences between both groups; however, two children in the placebo group suffered a recurrence of febrile UTI within 6 months of the follow-up period, while there were no recurrences of UTI in the probiotic group. In the test group, the number of febrile days after the initiation of antibiotics with probiotics was shorter, although not reaching statistical significance (p = 0.084). According to our results, probiotics might be helpful in alleviating UTI symptoms and in UTI prevention. Further research with a larger sample size is warranted. Additionally, basic scientific studies for the selection of proper immunobiotic strains of probiotics should be performed.

OBJECTIVE: The aim of this retrospective study was to investigate the impact of a broad spectrum of antihypertensive (AH) medications on urinary tract infections (UTI) of outpatients diagnosed in general practices in Germany.
METHODS: This study included a total of 367,960 patients aged ≥ 18 years newly a diagnosed with UTI in 1274 general practices in Germany between January 2010 and December 2019. The analysis was conducted for five groups representing five AH therapy classes (diuretics (DIU); beta blockers (BB); calcium channel blockers (CCB); ACE inhibitors (ACEi); angiotensin II receptor blockers (ARB)), each containing 73,592 patients. A Cox regression model was used to analyze the association between each antihypertensive drug class and UTI incidence as compared to all other antihypertensive drug classes (as a group).
RESULTS: The incidence of UTI diagnosis was slightly higher in patients treated with DIU (8.6%), followed by ACEi (8.1%), ARB (7.9%), and CCB (6.5%). Antibiotic therapy for UTI was given in 5.6% of DIU and 4.3% of CCB patients. The incidence of UTI and antibiotic therapy was much higher in women than in men across all therapy classes. No significant increase or decrease in UTI incidence or antibiotic therapy was observed in any of the AH therapy classes investigated.
CONCLUSIONS: The present study did not identify a significant increase or decrease of UTI incidence or antibiotic therapy in patients treated with ACEi, ACB, CCB, beta blockers or diuretics. Across all AH classes studied, the incidence of UTI and antibiotic therapy was higher in women than in men, although not significantly.

UNASSIGNED: Our study aimed to determine the etiology of urinary tract infections (UTIs), resistance profiles of isolated bacteria, and virulence factors of Escherichia coli associated with bacteriuria in diabetic patients in Ghana.
UNASSIGNED: Midstream urine samples from 982 diabetic patients were tested for uropathogens at the National Diabetes Management and Research Centre in Ghana, using standard bacteriological methods, with antibiogram testing of the isolates using the Kirby-Bauer disk diffusion, as per CLSI guidelines. Polymerase chain reaction (PCR) was used to investigate the phylogenetic groupings and virulence factor (VF) genes of isolated E. coli.
UNASSIGNED: The overall prevalence of UTIs was 9.2%, and the main uropathogens were Klebsiella spp. (55.6%) and Escherichia coli (31.3%). Age, duration of diabetes, and a previous history of UTIs were risk factors associated with UTI (p-value < 0.05). High levels of antibacterial resistance to cefuroxime (84%), ampicillin (80%), and gentamicin (70.7%) were observed. The distribution of VFs in each phylogenetic group revealed that sfa-iutA-KpsTMII-KpsTMIII genes were associated with group B2, and iutA-ibe were associated with group D.
UNASSIGNED: The isolated uropathogens were highly resistant, and the E. coli isolates possessed varying VFs. Continuous monitoring of bacteria associated with UTI in diabetics is highly recommended.

Although Sri Lanka belongs to a region with a high prevalence of extended-spectrum β-lactamase (ESBL), AmpC β-lactamase and carbapenemase-producing Enterobacteriaceae, data regarding antimicrobial resistance (AMR) is limited. We studied the prevalence and diversity of β-lactamases produced by Enterobacteriaceae urinary pathogens from two hospitals in the Western Province of Sri Lanka.
ESBL, AmpC β-lactamase and carbapenemase production was detected by phenotypic testing followed by genotyping.
The species responsible for urinary tract infections (UTI) were Escherichia coli (69%), Klebsiella pneumoniae (16%) and Enterobacter sp (6%). The prevalence of ESBL (50%), AmpC β-lactamase (19%) and carbapenemase (11%) phenotypes was high, and greater in hospital-acquired (HA-UTI) (75%) than in community-acquired UTI (CA-UTI) (42%). Identification of CA-UTI caused by carbapenemase-producing Enterobacteriaceae (5%) is alarming. Only one ESBL gene, blaCTX- M-15, was detected. AmpC β-lactamase genes found in E. coli and K. pneumoniae were blaCMY-2, blaCMY-42 and blaDHA-1, while Enterobacter sp. carried blaACT-1. Carbapenemase genes were blaNDM-1, blaNDM-4, blaOXA-181 and blaOXA-232, while blaKPC, blaIMP and blaVIM were absent. Co-occurrence of multiple bla genes, with some isolates harbouring six different bla genes, was common. Carbapenem-resistant isolates without carbapenemase genes displayed mutations in the outer membrane porin genes, ompF of E. coli and ompK36 of K. pneumoniae. Factors associated with UTI with β-lactamase-producing Enterobacteriaceae were age ≥50 years, previous hospitalization, presence of an indwelling urinary catheter, history of diabetes mellitus or other chronic illness and recurrent urinary tract infections.
This study adds to the currently scarce data on AMR in Sri Lanka.

Urinary tract infections caused by extended-spectrum β-lactamase Escherichia coli (ESBL-EC) are increasing worldwide and are a current concern because treatment options are often limited. This study investigated antimicrobial susceptibility, antimicrobial resistance genes (ARGs), and the biological diversity of urinary ESBL-EC isolates at Cerdanya Hospital, a European cross-border hospital that combines French and Spanish healthcare models. Bacterial identification and susceptibility were determined using the Microscan WalkAway® system and ESBL production was examined by the double-disk synergy method. Isolates were sequenced using the Ion S5™ next-generation sequencing system, with the whole-genome sequences then assembled using SPADEs software and analyzed using PubMLST, ResFinder, FimTyper, PlasmidFinder, and VirulenceFinder. A phylogenetic analysis was performed by constructing an assembly-based core-SNV alignment, followed by a phylogenetic tree constructed using Parsnp from the Harvest suite. All isolates studied were multidrug-resistant and could be classified into 19 different sequence types characterized by a high genetic diversity. The most prevalent ESBL-enzymes were CTX-M-14 and CTX-M-15. High-risk international clones (ST131, ST10, and ST405) were also identified. The results demonstrated the absence of a single predominant clone of ESBL-MDR-EC at Cerdanya Hospital.