Exploring the clinical and diagnostic value of metagenomic next-generation sequencing for urinary tract infection: a systematic review and meta-analysis.

BACKGROUND: A new pathogen detection tool, metagenomic next-generation sequencing (mNGS), has been widely used for infection diagnosis, but the clinical and diagnostic value of mNGS in urinary tract infection (UTI) remains inconclusive. This systematic review with meta-analysis aimed to investigate the efficacy of mNGS in treating UTIs. METHODS: A comprehensive literature search was performed in PubMed, Web of Science, Embase, and the Cochrane Library, and eligible studies were selected based on the predetermined criteria. The quality of the included studies was assessed via the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool, and the certainty of evidence (CoE) was measured by the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) score. Then, the positive detection rate (PDR), pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve of the summary receiver operating characteristic curve (AUROC) was estimated in Review Manager, Stata, and MetaDisc. Subgroup analysis, meta-regression, and sensitivity analysis were performed to reveal the potential factors that influence internal heterogeneity. RESULTS: A total of 17 studies were selected for further analysis. The PDR of mNGS was markedly greater than that of culture (odds ratio (OR) = 2.87, 95% confidence interval [CI]: 1.72-4.81, p < 0.001, I2 = 90%). The GRADE score presented a very low CoE. Then, the pooled sensitivity was 0.89 (95% CI: 0.86-0.91, I2 = 39.65%, p = 0.06), and the pooled specificity was 0.75 (95% CI: 0.51-0.90, I2 = 88.64%, p < 0.001). The AUROC of the studies analyzed was 0.89 (95% CI: 0.86-0.92). The GRADE score indicated a low CoE. CONCLUSION: The current evidence shows that mNGS has favorable diagnostic performance for UTIs. More high-quality prospective randomized controlled trials (RCTs) are expected to verify these findings and provide more information about mNGS in UTI treatment and prognosis.

A systematic review of recent advances in urinary tract infection interventions and treatment technology.

OBJECTIVE: Urinary tract infection is one of the most common extraintestinal infectious diseases encountered in clinics. It affects both genders and all age groups and constitutes a major health issue in clinical practice worldwide. Uropathogens often develop resistance to therapeutic agents, creating a formidable challenge for physicians to treat these infections. The goal of the current review is to provide current information on therapeutic advancements and interventions in the treatment of urinary tract infections. MATERIALS AND METHODS: Databases like MEDLINE, PubMed, and ClinicalTrials.gov were used as search engines to collect the relevant articles, and the required information was extracted. RESULTS: Research data suggest an increasing prevalence of pathogenic strains that are resistant to standard antimicrobial regimens recommended for the treatment of urinary tract infections. Targeted therapies for urinary tract infections, such as mannosides and pilicides, as well as vaccinations against uropathogenic Escherichia coli, have been developed recently. The efficacy of other strategies like iontophoresis, hydrogel-coated catheters, and antibiofilm therapy is also investigated. Clinical trials conducted between 2014 and 2019 show a rise in interest in a variety of therapies, highlighting the need for a thorough strategy to treat urinary tract infections, particularly in populations of women. CONCLUSIONS: Antimicrobial-resistant strains of Escherichia coli are becoming more common in urinary tract infections, which have led to the development of targeted medicines such as mannosides and pilicides, as well as immunizations against the pathogenic Escherichia coli strains. There is continuing research into alternate approaches, such as hydrogel-coated catheters, antibiofilm therapy, and iontophoresis. Clinical trials conducted between 2014 and 2019 showed a rise in interest in these different treatment approaches.

Development and evaluation of fermented milk with Lactobacillus acidophilus added to concentrated cranberry (Vaccinium macrocarpon) juice with the potential to minimize the recurrence of urinary tract infections.

Repeated urinary tract infections affect many people worldwide. A potential strategy to reduce the incidence of these infections is to consume probiotics and cranberry fruit regularly. In this context, this study aims to prepare fermented milk with Lactobacillus acidophilus La-5 added with concentrated cranberry juice in two concentrations (5 and 10 %, corresponding to C1 and C2 samples, respectively) and evaluate different technological aspects of the samples after production and during storage, and comparing with the control sample (C). The juice had pH 1.91, 70.09 % of solids, and total proanthocyanidins and A-type proanthocyanidins (PACs) values of 117.03 mg/100 g and 16.38 mg/100 g, respectively. The higher the juice content added to the product, the higher the acidity (1.4 and 2.6 g of lactic acid in 100 g, corresponding to C1 and C2 on day 1 (D1), respectively), the total proanthocyanidin content (1.96 and 4.01 mg/100 g on D1; and 1.31 and 3.05 mg/100 g on day 28 of storage (D28), corresponding to C1 and C2, respectively) and A-type proanthocyanidin (0.56 and 1.26 mg/100 g in Day 1; and 0.54 and 1.19 mg/100 g in D28, corresponding to C1 and C2, respectively), higher the values of the color parameters (L*a* and C*), and lower pH value, probiotic viability, and sensory acceptance. Furthermore, the rheological parameters demonstrated a stronger protein network due to the addition of cranberry. The new formulations, including samples C1 and C2, are alternatives as functional products, which regular consumption probably has the potential to minimize the recurrence of urinary tract infections.

Novel Fabrication of Bio-polymeric Nanogel Loaded with Nalidixic Acid Formulations for the Effective Prevention of Bacterial Pathogens Leading Urinary Tract Infection and Its Biosafety Evaluation.

Management of urinary tract infections (UTI) is a highly challenging process due to the biofilm-forming ability of human-pathogenic bacteria. Here, we designed to fabricate an effective nanogel with a combination of chitosan bio-polymer and nalidixic acid to prevent biofilm-forming bacterial pathogens. Chitosan-coated nalidixic acid nanogel (NA@CS) exhibits outstanding inhibition potential against bacterial strains. In vitro, anti-bacterial analysis methods (well diffusion, colony-forming assay, and anti-biofilm assay) were performed to study the bacterial inhibition potential of prepared nanogel, which reveals that NA@CS nanogel have greater inhibition potential against selected pathogens. The combination of nalidixic acid with chitosan biopolymer decreases the virulence and pathogenicity of biofilm-forming pathogens due to their ability to membrane phospholipids penetration. Furthermore, the fabricated NA@CS nanogel showed reliable in vitro bio-compatibility on L929 fibroblast cells and in vivo compatibility with Artemia salina animal model. Overall, the results demonstrate that NA@CS nanogel could be an effective therapeutic for treating urinary tract infections and urine bladder wound healing.

Urinary tract infection among people living with human immunodeficiency virus attending selected hospitals in Addis Ababa and Adama, central Ethiopia.

Background: Urinary tract infections (UTIs) and antibacterial resistance (ABR) are important public health problems, but they are not well-studied among people living with human immunodeficiency virus (PLHIV) globally, especially in low-income countries. Therefore, it is important to regularly measure the extent of UTIs and ABR in the most susceptible populations. This study aimed to investigate the prevalence of UTIs, associated factors, bacterial causal agents, and their antibiotic susceptibility profile among PLHIV in central Ethiopia. Methods: A hospital-based cross-sectional study was conducted to recruit 688 PLHIV by a simple random sampling method. Background information was gathered through interviews, while clinical information was gathered from recent information sheets of patient charts using organized, pretested, and validated study tools. Midstream urine was collected aseptically and transported to the Microbiology Laboratory of Aklilu Lemma Institute of Pathobiology within 4 h of collection, maintaining its cold chain. Standard conventional microbial culture methods and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry were used to identify the bacterial isolates at the species level. Kirby Bauer's disk diffusion method was used to determine the antibiotic susceptibility profile of the bacterial isolates based on the interpretation guidelines of the Clinical Laboratory Standard Institute. Logistic regression models were used to examine factors associated with the occurrence of UTIs among PLHIV attending selected hospitals in Addis Ababa, and Adama. Results: Out of 688 PLHIVs involved in the current study, 144 (20.9%) were positive for UTIs, whereas the majority were asymptomatic for UTIs. In the multivariable logistic regression analysis, only HIV RNA ≥ 200 copies/ml [AOR = 12.24 (95% CI, 3.24, 46.20), p < 0.01] and being symptomatic for UTIs during the study period [AOR = 11.57 (95% CI, 5.83, 22.97), p < 0.01] were associated with the occurrence of UTIs. The dominant bacterial species isolated were Escherichia coli (E. coli; n = 65; 43%), followed by Enterococcus faecalis (E. faecalis; n = 16; 10.6%) and Klebsiella pneumoniae (K. pneumoniae; n = 11; 7.3%). Over half of the E. coli isolates were resistant to antibiotics such as gentamicin (GM; n = 44; 67.7%), amikacin (AN; n = 46; 70.8%), nalidixic acid (NA; n = 42; 64.6%), ciprofloxacin (CIP; n = 40; 61.5%), and azithromycin (AZM; n = 45; 69.2%). All of the K. pneumoniae isolates (n = 11; 100%), (n = 6; 54.5%), and (n = 7; 63.6%) were resistant to [amoxicillin as well as amoxicillin + clavulanic acid], ceftriaxone, and sulfamethoxazole + trimethoprim, respectively. All the Staphylococcus aureus (S. aureus) isolates were resistant to cefoxitin, which implies methicillin-resistant S. aureus (MRSA). Conclusion: The high prevalence of UTIs and antibiotic resistance revealed in the current study needs public health interventions such as educating the population about preventive measures and the importance of early treatment of UTIs. Our findings also highlight the need to provide UTI screening services for PLHIV, and healthcare providers should adopt antibiotic stewardship programs to promote and ensure their appropriate and judicious use.

Reduction of misdiagnosis in urinary tract infections during pregnancy: The role of adjusted urine flow cytometry parameters.

INTRODUCTION: Urinary tract infections (UTIs) pose a significant health concern, particularly among pregnant women, for whom accurate diagnosis is essential. However, the use of Urine flow cytometry (UF) for detecting UTIs in this demographic often results in misdiagnosis. The objective of this study was to explore the reasons behind these diagnostic errors and to develop a strategy to minimize the rate of UTI misdiagnosis in pregnant women. MATERIAL AND METHODS: The study enrolled 1,200 women aged 18 to 40 years, categorized into pregnant and non-pregnant groups. UTIs were diagnosed using urine bacterial culture, microscopic examination, and UF, followed by statistical analysis to identify any discrepancies in diagnosis between the groups. Following the calibration of UF analyzer's parameters, the most effective CR(WBC)-CW-FSC-P Gain setting for diagnosing UTIs in pregnant women through UF was ascertained by applying the Youden index. RESULTS: The clinical diagnosis rate of UTIs was significantly higher in pregnant women (40.91%) compared to non-pregnant women (20.26%). However, urine microscopy and bacterial culture showed no significant difference in the rates of UTIs between the two groups, suggesting a potential for misdiagnosis. The false-positive rate for WBCs detected by UF was 30.43%, and adjusting the CR(WBC)-CW-FSC-P Gain value of UF reduced the false-positive rate to 9.45%. CONCLUSION: The incidence of UTIs in pregnant women may be overestimated because of the limitations inherent to UF. Adjusting the parameters of the UF analyzer, particularly the CR(WBC)-CW-FSC-P Gain value, can significantly reduce the rate of UTI misdiagnosis in pregnant women.

Investigating the interaction of zno nanoparticles with flagellum and fimbriae in multi-drug resistant uropathogenic bacteria encoding fli and fim genes.

Due to the increasing occurrence of drug resistant urinary tract infections (UTI) among children, there is a need to investigate alternative effective treatment protocols such as nanoparticles. Flagella and fimbriae are primary factors contributing the virulence of urinary tract infecting bacteria. The aim of this study was to assess the antibacterial effects of zinc oxide nanoparticles which have been synthesized using both chemical and green methods on multi-drug resistant (MDR) uropathogenic bacteria encoding fli and fim genes and investigating their binding ability to bacterial appendage proteins. A total of 30 urine culture samples were collected from children under 2 years old diagnosed with urinary tract infection. The isolates underwent antibiotic suseptibility assessment and the isolates demonstrating MDR were subjected to molecular amplification of fimG (fimbrial) and fliD and fliT (flagellal) genes. The confirmation of cellular appendages was achieved through silver nitrate staining. The antibacterial efficacy of the synthetized nanoparticles was assessed using the micro and macrodilution methods. The successful binding of nanoparticles to bacterial appendage proteins was confirmed through mobility shift and membrane filter assays. The dimensions of chemically synthesized ZnO nanoparticles and green nanoparticles were measured at 30 nm and 85 nm, respectively, with the exhibition of hexagonal geometries. The nanoparticles synthesized through chemical and green methods exhibited minimum inhibitory concentrations (MIC) of 0.0062-0.025 g/L and 0.3 g/L, respectively. The ability of ZnO nanoparticles to bind bacterial appendage proteins and to combat MDR uropathogenic bacteria are promising for new treatment protocols against UTI in children in future.

Efficacy and safety of preventing catheter-associated urinary tract infection by inhibiting catheter bacterial biofilm formation: a multicenter randomized controlled trial.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) remains the most significant challenge among hospital-acquired infections (HAIs), yet still unresolved. The present study aims to evaluate the preventive effectiveness of JUC Spray Dressing (name of U.S. FDA and CE certifications, while the medical device name in China is Long-acting Antimicrobial Material) alone for CAUTI without combining with antibiotics and to evaluate the impact of bacterial biofilm formation on CAUTI results on the inserted catheters of patients. METHODS: In this multicenter, randomized, double-blind study, we enrolled adults who suffered from acute urinary retention (AUR) and required catheterization in 6 hospitals in China. Participants were randomly allocated 1:1 according to a random number table to receive JUC Spray Dressing (JUC group) or normal saline (placebo group). The catheters were pretreated with JUC Spray Dressing or normal saline respectively before catheterization. Urine samples and catheter samples were collected after catheterization by trial staff for further investigation. RESULTS: From April 2012 to April 2020, we enrolled 264 patients and randomly assigned them to the JUC group (n = 132) and the placebo group (n = 132). Clinical symptoms and urine bacterial cultures showed the incidence of CAUTI of the JUC group was significantly lower than the placebo group (P < 0.01). In addition, another 30 patients were enrolled to evaluate the biofilm formation on catheters after catheter insertion in the patients' urethra (10 groups, 3 each). The results of scanning electron microscopy (SEM) showed that bacterial biofilm formed on the 5th day in the placebo group, while no bacterial biofilm formed on the 5th day in the JUC group. In addition, no adverse reactions were reported using JUC Spray Dressing. CONCLUSION: Continued indwelling urinary catheters for 5 days resulted in bacterial biofilm formation, and pretreatment of urethral catheters with JUC Spray Dressing can prevent bacterial biofilm formation by forming a physical antimicrobial film, and significantly reduce the incidence of CAUTI. This is the first report of a study on inhibiting bacterial biofilm formation on the catheters in CAUTI patients.

The role of bacterial size, shape and surface in macrophage engulfment of uropathogenic E. coli cells.

Uropathogenic Escherichia coli (UPEC) can undergo extensive filamentation in the host during acute urinary tract infections (UTIs). It has been hypothesised that this morphological plasticity allows bacteria to avoid host immune responses such as macrophage engulfment. However, it is still unclear what properties of filaments are important in macrophage-bacteria interactions. The aim of this work was to investigate the contribution of bacterial biophysical parameters, such as cell size and shape, and physiological parameters, such as cell surface and the environment, to macrophage engulfment efficiency. Viable, reversible filaments of known lengths and volumes were produced in the UPEC strain UTI89 using a variety of methods, including exposure to cell-wall targeting antibiotics, genetic manipulation and isolation from an in vitro human bladder cell model. Quantification of the engulfment ability of macrophages using gentamicin-protection assays and fluorescence microscopy demonstrated that the ability of filaments to avoid macrophage engulfment is dependent on a combination of size (length and volume), shape, cell surface and external environmental factors. UTI89 filamentation and macrophage engulfment efficiency were also found to occur independently of the SOS-inducible filamentation genes, sulA and ymfM in both in vivo and in vitro models of infection. Compared to filaments formed via antibiotic inhibition of division, the infection-derived filaments were preferentially targeted by macrophages. With several strains of UPEC now resistant to current antibiotics, our work identifies the importance of bacterial physiological and morphological states during infection.

Neutrophil extracellular traps protect the kidney from ascending infection and are required for a positive leukocyte dipstick test.

Lower urinary tract infection (UTI) is common but only rarely complicated by pyelonephritis. However, the mechanisms preventing extension to the kidney are unclear. Here, we identified neutrophil extracellular traps (NETs) in healthy human urine that provide an antibacterial defense strategy within the urinary tract. In both in vivo murine models of UTI where uropathogenic E. coli are inoculated into the bladder and ex vivo human urine models, NETs interacted with uromodulin to form large webs that entrapped the bacteria. Peptidyl arginine deiminase 4 (PADI4) inhibition in mice blocked NETosis and resulted in progression of cystitis into pyelonephritis, suggesting that NETosis of urinary neutrophils acts to prevent bacterial ascent into the kidney. Analysis of UK Biobank data revealed that genetic variants in PADI4 that associated with increased risk of rheumatoid arthritis in multiple genome-wide association studies were consistently associated with reduced susceptibility to UTI. Last, we showed that urine dipstick testing for leukocyte esterase was negative in the presence of intact blood neutrophils but became positive when neutrophils were stimulated to NET, and this could be prevented by selective PADI4 inhibition, demonstrating that this test does not detect absolute neutrophil count, as has long been assumed, but specifically detects neutrophils that have undergone NETosis. These findings highlight the role of NETosis in preventing ascending infections in the urinary tract and improve our understanding of one of the most common clinical tests in medicine.

UNAM-HIMFG Bacterial Lysate Activates the Immune Response and Inhibits Colonization of Bladder of Balb/c Mice Infected with the Uropathogenic CFT073 Escherichia coli Strain.

Urinary tract infections (UTIs) represent a clinical and epidemiological problem of worldwide impact that affects the economy and the emotional state of the patient. Control of the condition is complicated due to multidrug resistance of pathogens associated with the disease. Considering the difficulty in carrying out effective treatment with antimicrobials, it is necessary to propose alternatives that improve the clinical status of the patients. With this purpose, in a previous study, the safety and immunostimulant capacity of a polyvalent lysate designated UNAM-HIMFG prepared with different bacteria isolated during a prospective study of chronic urinary tract infection (CUTI) was evaluated. In this work, using an animal model, results are presented on the immunostimulant and protective activity of the polyvalent UNAM-HIMFG lysate to define its potential use in the control and treatment of CUTI. Female Balb/c mice were infected through the urethra with Escherichia coli CFT073 (UPEC O6:K2:H1) strain; urine samples were collected before the infection and every week for up to 60 days. Once the animals were colonized, sublingual doses of UNAM-HIMFG lysate were administrated. The colonization of the bladder and kidneys was evaluated by culture, and their alterations were assessed using histopathological analysis. On the other hand, the immunostimulant activity of the compound was analyzed by qPCR of spleen mRNA. Uninfected animals receiving UNAM-HIMFG lysate and infected animals administered with the physiological saline solution were used as controls. During this study, the clinical status and evolution of the animals were evaluated. At ninety-six hours after infection, the presence of CFT073 was identified in the urine of infected animals, and then, sublingual administration of UNAM-HIMFG lysate was started every week for 60 days. The urine culture of mice treated with UNAM-HIMFG lysate showed the presence of bacteria for three weeks post-treatment; in contrast, in the untreated animals, positive cultures were observed until the 60th day of this study. The histological analysis of bladder samples from untreated animals showed the presence of chronic inflammation and bacteria in the submucosa, while tissues from mice treated with UNAM-HIMFG lysate did not show alterations. The same analysis of kidney samples of the two groups (treated and untreated) did not present alterations. Immunostimulant activity assays of UNAM-HIMFG lysate showed overexpression of TNF-α and IL-10. Results suggest that the lysate activates the expression of cytokines that inhibit the growth of inoculated bacteria and control the inflammation responsible for tissue damage. In conclusion, UNAM-HIMFG lysate is effective for the treatment and control of CUTIs without the use of antimicrobials.

Nur77 protects the bladder urothelium from intracellular bacterial infection.

Intracellular infections by Gram-negative bacteria are a significant global health threat. The nuclear receptor Nur77 (also called TR3, NGFI-B, or NR4A1) was recently shown to sense cytosolic bacterial lipopolysaccharide (LPS). However, the potential role for Nur77 in controlling intracellular bacterial infection has not been examined. Here we show that Nur77 protects against intracellular infection in the bladder by uropathogenic Escherichia coli (UPEC), the leading cause of urinary tract infections (UTI). Nur77 deficiency in mice promotes the formation of UPEC intracellular bacterial communities (IBCs) in the cells lining the bladder lumen, leading to persistent infection in bladder tissue. Conversely, treatment with a small-molecule Nur77 agonist, cytosporone B, inhibits invasion and enhances the expulsion of UPEC from human urothelial cells in vitro, and significantly reduces UPEC IBC formation and bladder infection in mice. Our findings reveal a new role for Nur77 in control of bacterial infection and suggest that pharmacologic agonism of Nur77 function may represent a promising antibiotic-sparing therapeutic approach for UTI.

A comparative study on the effects of doxycycline, nalidixic acid and meropenem on Escherichia coli in inducing urinary tract infections.

Urinary tract infections are widely recognized as prevalent bacterial infections frequently encountered in both hospital and community settings. The most common gram-negative bacterial pathogen in humans, extra-intestinal pathogenic Escherichia coli, causes these diseases. A retrospective cross-sectional study in Karachi, Pakistan examined Escherichia coli's susceptibility to doxycycline, nalidixic acid and meropenem. One hundred isolates of Escherichia coli from urine samples of patients were collected. The Kirby Bauer disc diffusion testing method was used following CLSI guidelines. The results showed variability because of differences in patient's gender and age. 84 out of 100 samples were of females and 16 samples were of males. Infection prevalence by age showed that 15% of isolates were from children (0-12 years), 2% from adolescents (13-18 years), 52% from adults (19-59 years) and 31% from seniors. This study concluded that females and adults (aged 19-59 years) are at highest risk of prevalence. Meropenem is a potential antibiotic choice for urinary tract infections due to its demonstrated 100% susceptibility. However, in light of increasing resistance trends, the administration of doxycycline and nalidixic acid should be reserved until antimicrobial susceptibility testing has been conducted. The study ensures that antibiotics are used judiciously and effectively in combating urinary tract infections while minimizing the risk of further antimicrobial resistance development.

Best Practices in Treatment of Fungal Urinary Tract Infections.

Fungal pathogens within the urine, specifically Candida species, are a common finding amongst hospitalized patients. Risk factors for the development of candiduria involve patients with indwelling urinary drainage devices, surgical patients, patients undergoing urologic instrumentation, and diabetic patients. Candiduria often presents with an asymptomatic course but can also be a severe life-threatening process. This article will review the epidemiology and risk factors associated with fungal urinary tract infections, and the diagnosis and categorization of these infections along with a review of current medical and surgical treatments for this condition.

Manipulating the Gut Microbiome in Urinary Tract Infection-Prone Patients.

Although antibiotics remain the mainstay of urinary tract infection treatment, many affected women can be caught in a vicious cycle in which antibiotics given to eradicate one infection predispose them to develop another. This effect is primarily mediated by disturbances in the gut microbiome that both directly enrich for uropathogenic overgrowth and induce systemic alterations in inflammation, tissue permeability, and metabolism that also decrease host resistance to infection recurrences. Here, we discuss nonantibiotic approaches to manipulating the gut microbiome to reverse the systemic consequences of antibiotics, including cranberry supplementation and other dietary approaches, probiotic administration, and fecal microbiota transplantation.

Clinical Microbiome Testing for Urology.

The urine culture is imperfect, and a series of alternative approaches are in development to assist in diagnosis, treatment, and prevention of urinary tract infection (UTI). Culture-independent approaches typically do not distinguish between viable and nonviable bacteria, and are generally not included in current clinical guidance. Next-generation sequencing may play an important future role in precise targeting of antibiotic treatment of asymptomatic bacteriuria prior to endourologic surgery or in pregnancy. Future studies are needed to determine whether microbiota modulation could prevent UTI. Possible modulation mechanisms may include fecal microbiota transplant, application of topical vaginal estrogen or probiotics, and bacteriophage therapy.

Advances in the Treatment of Urinary Tract Infection and Bacteriuria in Pregnancy.

Understanding the management of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) during pregnancy is important, given the prevalence of these conditions, associated risks to the mother and fetus /newborn, and potential requirement for antibiotic treatment. Screening for ASB with a urine culture is required during pregnancy, and a positive culture is treated for 5 to 7 days with culture-specific antibiotics. Recent research on non-antibiotic prevention and shortened duration of antibiotic treatment may offer a slightly different approach to ASB and UTI in pregnancy.

Conformational ensembles in Klebsiella pneumoniae FimH impact uropathogenesis.

Klebsiella pneumoniae is an important pathogen causing difficult-to-treat urinary tract infections (UTIs). Over 1.5 million women per year suffer from recurrent UTI, reducing quality of life and causing substantial morbidity and mortality, especially in the hospital setting. Uropathogenic E. coli (UPEC) is the most prevalent cause of UTI. Like UPEC, K. pneumoniae relies on type 1 pili, tipped with the mannose-binding adhesin FimH, to cause cystitis. However, K. pneumoniae FimH is a poor binder of mannose, despite a mannose-binding pocket identical to UPEC FimH. FimH is composed of two domains that are in an equilibrium between tense (low-affinity) and relaxed (high-affinity) conformations. Substantial interdomain interactions in the tense conformation yield a low-affinity, deformed mannose-binding pocket, while domain-domain interactions are broken in the relaxed state, resulting in a high-affinity binding pocket. Using crystallography, we identified the structural basis by which domain-domain interactions direct the conformational equilibrium of K. pneumoniae FimH, which is strongly shifted toward the low-affinity tense state. Removal of the pilin domain restores mannose binding to the lectin domain, thus showing that poor mannose binding by K. pneumoniae FimH is not an inherent feature of the mannose-binding pocket. Phylogenetic analyses of K. pneumoniae genomes found that FimH sequences are highly conserved. However, we surveyed a collection of K. pneumoniae isolates from patients with long-term indwelling catheters and identified isolates that possessed relaxed higher-binding FimH variants, which increased K. pneumoniae fitness in bladder infection models, suggesting that long-term residence within the urinary tract may select for higher-binding FimH variants.

Dietary influences on urinary tract infections: unraveling the gut microbiota connection.

This study employs Mendelian randomization to investigate the causal relationships between dietary factors, gut microbiota, and urinary tract infections (UTIs). Our analysis revealed statistically significant associations, including high alcohol intake, cheese, and oily fish consumption with UTI risk, as well as links between UTI risk and specific gut microbiota, such as Prevotellaceae, Butyrivibrio, Anaerotruncus, and Dorea. Additionally, we observed associations with inflammatory markers, including C-Reactive Protein and Interleukin-6. Although the observed effects of these dietary factors on UTI risk are minimal and may limit their clinical relevance, these findings can still hold significant implications at the population level in public health. This research offers novel insights into the interplay between diet, gut microbiota, and UTI risk, laying a foundation for future studies. Further research is warranted to validate these associations and to explore the underlying mechanisms and their broader impact on public health.