Inhibiting Host Protein Deposition on Urinary Catheters Reduces Urinary Tract Infections
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Enterococcus Faecalis (ncbitaxon:1351) Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Ana Lidia Flores-Mireles Marissa Jeme Andersen Matthew Champion
PROVIDER: MSV000088527 | MassIVE | Mon Dec 06 12:41:00 GMT 2021
REPOSITORIES: MassIVE
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Project description:Chronic bacterial infections on medical devices, including catheter-associated urinary tract infections (CAUTI), are associated with bacterial biofilm communities that are refractory to antibiotic therapy and resistant to host immunity. Previously, we have shown that Pseudomonas aeruginosa can cause CAUTI by forming a device-associated biofilm that is independent of known biofilm exopolysaccharides. Here, we show by RNA-seq that host urine alters the transcriptome of P. aeruginosa by suppressing quorum sensing regulated genes. P. aeruginosa produces acyl homoserine lactones (AHLs) in the presence of urea, but cannot perceive AHLs. Repression of quorum sensing by urine implies that quorum sensing should be dispensable during infection of the urinary tract. Indeed, mutants defective in quorum sensing are able to colonize similarly to wild-type in a murine model of CAUTI. Quorum sensing-regulated processes in clinical isolates are also inhibited by urea. These data show that urea in urine is a natural anti-quorum sensing mechanism in mammals.
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Project description:The present study investigated the incidence of hyperammonemia in urinary tract infections and explored the utility of urinary obstruction relief and antimicrobial administration to improve hyperammonemia.This was an observational study. Subjects were patients who were diagnosed with urinary tract infection and hospitalized between June 2008 and June 2009. We measured plasma ammonia levels on admission in patients who were clinically diagnosed with urinary tract infection and hospitalized. We assessed each patient's level of consciousness on admission using the Glasgow Coma Scale (GCS) and performed urine and blood cultures. We also assessed hearing prior to hospitalization using the Eastern Cooperative Oncology Group performance status (ECOG-PS). In cases with high ammonia levels on admission, plasma ammonia and GCS were measured 24 hours and 5-7 days later.Sixty-seven candidates were enrolled; of these, 60 cases (89.6%) with bacterial cell counts ≥10(4) CFU/mL were studied. Five cases (8.3%) presented with high plasma ammonia levels. Cases with hyperammonemia were significantly more likely to present with low GCS scores and urinary retention rate. All five cases received antimicrobial therapy with an indwelling bladder catheter to relieve urinary retention. The case 5 patient died shortly after admission due to complicated aspiration pneumonia; in the remaining cases, plasma ammonia levels were rapidly normalized and the level of consciousness improved.The occurrence of hyperammonemia in urinary tract infections is not rare. The cause of hyperammonemia is urinary retention obstruction. Therefore, along with antimicrobial administration, relief of obstruction is important for the treatment of hyperammonemia caused by this mechanism.
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Project description:Urinary tract infections (UTIs) are common, recurrent infections that can be mild to life-threatening. The continued emergence of antibiotic resistance, together with our increasing understanding of the detrimental effects conferred by broad-spectrum antibiotic use on the health of the beneficial microbiota of the host, has underscored the weaknesses in our current treatment paradigm for UTIs. In this Review, we discuss how recent microbiological, structural, genetic and immunological studies have expanded our understanding of host-pathogen interactions during UTI pathogenesis. These basic scientific findings have the potential to shift the strategy for UTI treatment away from broad-spectrum antibiotics targeting conserved aspects of bacterial replication towards pathogen-specific antibiotic-sparing therapeutics that target core determinants of bacterial virulence at the host-pathogen interface.
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Project description:The urinary tract is constantly exposed to different microorganisms that colonize the gastrointestinal tract and the urinary tract is normally well prepared to resist infections by these microorganisms. This resistance to infection is mainly accomplished by the versatility of the immune system in the urinary tract, with both innate and adaptive immune responses. With the increasing knowledge of how the immune system works in the urinary tract and also the recognition of the virulence attributes of uropathogens, several potentially effective and tailored strategies to contain or prevent urinary tract infections have emerged.
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Project description:A urinary tract infection (UTI) is a collective term for infections that involve any part of the urinary tract. It is one of the most common infections in local primary care. The incidence of UTIs in adult males aged under 50 years is low, with adult women being 30 times more likely than men to develop a UTI. Appropriate classification of UTI into simple or complicated forms guides its management and the ORENUC classification can be used. Diagnosis of a UTI is based on a focused history, with appropriate investigations depending on individual risk factors. Simple uncomplicated cystitis responds very well to oral antibiotics, but complicated UTIs may require early imaging, and referral to the emergency department or hospitalisation to prevent urosepsis may be warranted. Escherichia coli remains the predominant uropathogen in acute community-acquired uncomplicated UTIs and amoxicillin-clavulanate is useful as a first-line antibiotic. Family physicians are capable of managing most UTIs if guided by appropriate history, investigations and appropriate antibiotics to achieve good outcomes and minimise antibiotic resistance.
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Project description:Ribonuclease 7 (RNase 7) is an antimicrobial peptide that prevents urinary tract infections (UTI); however, it is yet unknown how RNASE7 genetic variations affect its antimicrobial activity and its mitigation of UTI risk. This study determined whether the RNASE7 SNP rs1263872 is more prevalent in children with UTI and defined how rs1263872 affects RNase 7's antimicrobial activity against uropathogenic E. coli (UPEC). We performed genotyping for rs1263872 in 2 national UTI cohorts, including children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux trial or the Careful Urinary Tract Infection Evaluation study. Genotypes from these cohorts were compared with those of female controls with no UTI. To assess whether rs1263872 affects RNase 7's antimicrobial activity, we generated RNase 7 peptides and genetically modified urothelial cultures encoding wild-type RNase 7 and its variant. Compared with controls, girls in both UTI cohorts had an increased prevalence of the RNASE7 variant. Compared with the missense variant, wild-type RNase 7 peptide showed greater bactericidal activity against UPEC. Wild-type RNase 7 overexpression in human urothelial cultures reduced UPEC invasive infection compared with mutant overexpression. These results show that children with UTI have an increased prevalence of RNASE7 rs1263872, which may increase UTI susceptibility by suppressing RNase 7's antibacterial activity.
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Project description:Proteus mirabilis is a Gram-negative bacterium and is well known for its ability to robustly swarm across surfaces in a striking bulls'-eye pattern. Clinically, this organism is most frequently a pathogen of the urinary tract, particularly in patients undergoing long-term catheterization. This review covers P. mirabilis with a focus on urinary tract infections (UTI), including disease models, vaccine development efforts, and clinical perspectives. Flagella-mediated motility, both swimming and swarming, is a central facet of this organism. The regulation of this complex process and its contribution to virulence is discussed, along with the type VI-secretion system-dependent intra-strain competition, which occurs during swarming. P. mirabilis uses a diverse set of virulence factors to access and colonize the host urinary tract, including urease and stone formation, fimbriae and other adhesins, iron and zinc acquisition, proteases and toxins, biofilm formation, and regulation of pathogenesis. While significant advances in this field have been made, challenges remain to combatting complicated UTI and deciphering P. mirabilis pathogenesis.
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Project description:BackgroundCranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections. The aim of this review is to assess the effectiveness of cranberries in treating such infections.ObjectivesTo assess the effectiveness of cranberries for the treatment of urinary tract infections.Search strategyThe search strategy developed by the Cochrane Renal Group was used. Also, companies involved with the promotion and distribution of cranberry preparations were contacted; electronic databases and the Internet were searched using English and non English language terms; reference lists of review articles and relevant trials were also searched.Selection criteriaAll randomised or quasi randomised controlled trials of cranberry juice or cranberry products for the treatment of urinary tract infections. Trials of men, women or children were included.Data collection and analysisTitles and abstracts of studies that were potentially relevant to the review were screened by one reviewer, RJ, who discarded studies that were clearly ineligible but aimed to be overly inclusive rather than risk losing relevant studies. Reviewers RJ and LM independently assessed whether the studies met the inclusion criteria. Further information was sought from the authors where papers contained insufficient information to make a decision about eligibility.Main resultsNo trials were found which fulfilled all of the inclusion criteria. Two trials were excluded because they did not have any relevant outcomes.Reviewer's conclusionsAfter a thorough search, no randomised trials which assessed the effectiveness of cranberry juice for the treatment of urinary tract infections were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of urinary tract infections. Well-designed parallel group, double blind trials comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating urinary tract infections are needed. Outcomes should include reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. Dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these trials.
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Project description:Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in their urovirulence, that is, their ability to infect the bladder in a mouse model of cystitis. We found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the E. coli strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and metabolism, could be used to predict subsequent colonization of the mouse bladder. Together, our findings suggest that UTI risk and outcome may be determined by complex interactions between host susceptibility and the urovirulence potential of diverse bacterial strains.
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Project description:Previous studies have suggested a link between urinary tract infections (UTIs) and cognitive impairment. One possible contributing factor for UTI-induced cognitive changes that has not yet been investigated is a potential alteration in hippocampal neurogenesis. In this study, we aim to investigate the effect of UTI on brain plasticity by specifically examining alterations in neurogenesis. Adult male Sprague Dawley rats received an intra-urethral injection of an Escherichia coli (E. coli) clinical isolate (108 CFU/mL). We found that rats with a UTI (CFU/mL ≥ 105) had reduced proliferation of neural stem cells (NSCs) at an early time point post infection (day 4) and neurogenesis at a later time point (day 34). This was associated with the decreased expression in mRNA of BDNF, NGF, and FGF2, and elevated expression of IL-1β in the hippocampus at 6 h post infection, but with no changes in optical intensity of the microglia and astrocytes. In addition, infected rats spent less time exploring a novel arm in the Y-maze test. Treatment with an anti-inflammatory drug did not revert the effect on NSCs, while treatment with antibiotics further decreased the basal level of their proliferation. This study presents novel findings on the impact of urinary tract infections on hippocampal neurogenesis that could be correlated with cognitive impairment.
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