Peptidoglycan endopeptidase MepM of uropathogenic Escherichia coli contributes to competitive fitness during urinary tract infections.

BACKGROUND: Urinary tract infections (UTIs) are common bacterial infections, primarily caused by uropathogenic Escherichia coli (UPEC), leading to significant health issues and economic burden. Although antibiotics have been effective in treating UPEC infections, the rise of antibiotic-resistant strains hinders their efficacy. Hence, identifying novel bacterial targets for new antimicrobial approaches is crucial. Bacterial factors required for maintaining the full virulence of UPEC are the potential target. MepM, an endopeptidase in E. coli, is involved in the biogenesis of peptidoglycan, a major structure of bacterial envelope. Given that the bacterial envelope confronts the hostile host environment during infections, MepM's function could be crucial for UPEC's virulence. This study aims to explore the role of MepM in UPEC pathogenesis. RESULTS: MepM deficiency significantly impacted UPEC's survival in urine and within macrophages. Moreover, the deficiency hindered the bacillary-to-filamentous shape switch which is known for aiding UPEC in evading phagocytosis during infections. Additionally, UPEC motility was downregulated due to MepM deficiency. As a result, the mepM mutant displayed notably reduced fitness in causing UTIs in the mouse model compared to wild-type UPEC. CONCLUSIONS: This study provides the first evidence of the vital role of peptidoglycan endopeptidase MepM in UPEC's full virulence for causing UTIs. MepM's contribution to UPEC pathogenesis may stem from its critical role in maintaining the ability to resist urine- and immune cell-mediated killing, facilitating the morphological switch, and sustaining motility. Thus, MepM is a promising candidate target for novel antimicrobial strategies.

Advances in uremic toxin detection and monitoring in the management of chronic kidney disease progression to end-stage renal disease.

Patients with end-stage kidney disease (ESKD) rely on dialysis to remove toxins and stay alive. However, hemodialysis alone is insufficient to completely remove all/major uremic toxins, resulting in the accumulation of specific toxins over time. The complexity of uremic toxins and their varying clearance rates across different dialysis modalities poses significant challenges, and innovative approaches such as microfluidics, biomarker discovery, and point-of-care testing are being investigated. This review explores recent advances in the qualitative and quantitative analysis of uremic toxins and highlights the use of innovative methods, particularly label-mediated and label-free surface-enhanced Raman spectroscopy, primarily for qualitative detection. The ability to analyze uremic toxins can optimize hemodialysis settings for more efficient toxin removal. Integration of multiple omics disciplines will also help identify biomarkers and understand the pathogenesis of ESKD, provide deeper understanding of uremic toxin profiling, and offer insights for improving hemodialysis programs. This review also highlights the importance of early detection and improved understanding of chronic kidney disease to improve patient outcomes.

Rapid intervention team strategy improves intervention quality for patients undergoing hemodialysis with arteriovenous shunt dysfunction or failure.

BACKGROUND: Vascular access dysfunction is a great burden for hemodialysis patients. Early intervention of a dysfunctional arteriovenous shunt is associated with higher technical success and may improve midterm patency. This trial aimed to estimate the feasibility of a new system, the "rapid intervention team" (RIT) strategy. METHODS: We recruited hemodialysis patients who visited our hospital because of arteriovenous shunt dysfunction or failure to undergo an RIT strategy from September 1, 2019 to December 31, 2022. In addition, we included a control group comprising patients who underwent percutaneous intervention for arteriovenous shunt dysfunction or failure before this strategy was implemented from February 1, 2017 to December 31, 2022. Case number, time to intervention, all-cause mortality, cumulative survival rate, and number of patients who required temporary dialysis catheter insertion and recreation were compared between the two groups. The primary endpoints were double-lumen insertion, a composite outcome involving permanent catheter insertion, and the need for recreation. The secondary endpoint was all-cause mortality. RESULTS: We enrolled 1054 patients, including 544 (51.6%) and 510 (48.4%) in the RIT and control groups, respectively. Even with the coronavirus disease of 2019 (COVID-19) pandemic, the number of cases significantly increased after the implementation of the RIT strategy (from 216 in 2019 to 828 in 2022, p for trend <0.001). The RIT group had a shortened time to intervention ( p for trend <0.001). The implementation of the RIT strategy was significantly associated with a reduced risk of insertion of a temporary double-lumen catheter and recreation of vascular access (1% vs 6% and 1% vs 28%, respectively; both p < 0.01). The cumulative survival rate was not significantly different between the RIT and control groups ( p = 0.16). CONCLUSION: The implementation of the RIT strategy improves the quantity and quality of percutaneous transluminal intervention for arteriovenous shunt dysfunction or failure in patients undergoing hemodialysis.

Late creation of vascular access increased post-hemodialysis mortality, hospitalization, and health-care expenditure: A population-based cohort study in Taiwan.

BACKGROUND/PURPOSE: The optimal timing of vascular access (VA) creation for hemodialysis (HD) and whether this timing affects mortality and health-care utilization after HD initiation remain unclear. Thus, we conducted a population-based study to explore their association. METHODS: We used Taiwan's National Health Insurance Research Database to analyze health-care outcomes and utilization in a cohort initiating HD during 2003-2013. We stratified patients by the following VA creation time points: >180, 91-180, 31-90, and ≤30 days before and ≤30 days after HD initiation and examined all-cause mortality, ambulatory care utilization/costs, hospital admission/costs, and total expenditure within 2 years after HD. Cox regression, Poisson regression, and general linear regression were used to analyze mortality, health-care utilization, and costs respectively. RESULTS: We identified 77,205 patients who started HD during 2003-2013. Compared with the patients undergoing VA surgery >180 days before HD initiation, those undergoing VA surgery ≤30 days before HD initiation had the highest mortality-15.92 deaths per 100-person-years, crude hazard ratio (HR) 1.56, and adjusted HR 1.28, the highest hospital admissions rates- 2.72 admission per person-year, crude rate ratio (RR) 1.48 and adjusted RR 1.32, and thus the highest health-care costs- US$31,390 per person-year, 7% increase of costs and 6% increase with adjustment within the 2-year follow-up after HD initiation. CONCLUSIONS: Late VA creation for HD can increase all-cause mortality, hospitalization, and health-care costs within 2 years after HD initiation. Early preparation of VA has the potential to reduce post-HD mortality and healthcare expenses for the ESKD patients.

A longitudinal epidemiology study of fluoroquinolone-nonsusceptible Klebsiella pneumoniae reveals an increasing prevalence of qnrB and qnrS in Taiwan.

BACKGROUND: Our objective was to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR) genes in fluoroquinolone-nonsusceptible Klebsiella pneumoniae (FQNSKP) in Taiwan, 1999-2022. METHODS: A total of 938 FQNSKP isolates were identified from 1966 isolates. The presence of PMQR and virulence genes, antimicrobial susceptibility, capsular types, and PMQR-plasmid transferability were determined. RESULTS: An increasing number of PMQR-containing FQNSKP isolates were observed over the study period. Our results showed that 69.0% (647 isolates) of FQNSKP isolates contained at least one PMQR gene, and 40.6%, 37.0%, and 33.9% of FQNSKP carried aac(6')-Ib-cr, qnrB, and qnrS, respectively. None of FQNSKP carried qepA and qnrC. The most common combination of PMQR genes was aac(6')-Ib-cr and qnrB (12.3%). The presence of PMQR genes is strongly related to resistance to aminoglycoside, cephalosporin, tetracycline, and sulfamethoxazole/trimethoprim in FQNSKP. The capsular serotype K64 is the most common serotype we tested in both the non-PMQR and PMQR FQNSKP isolates, while K20 showed a higher prevalence in PMQR isolates. The magA and peg-344 genes showed a significantly higher prevalence rate in non-PMQR isolates than in PMQR isolates. Eleven isolates that carried the PMQR and carbapenemase genes were identified; however, three successful transconjugants showed that the PMQR and carbapenemase genes were not located on the same plasmid. CONCLUSIONS: Our results indicated an increasing prevalence of PMQR genes, especially qnrB and qnrS, in FQNSKP in Taiwan. Moreover, the distribution of PMQR genes was associated with capsular serotypes and antimicrobial resistance gene and virulence gene distribution in FQNSKP.

A 24-year longitudinal study of Klebsiella pneumoniae isolated from patients with bacteraemia and urinary tract infections reveals the association between capsular serotypes, antibiotic resistance, and virulence gene distribution.

Longitudinal studies on the variations of phenotypic and genotypic characteristics of K. pneumoniae across two decades are rare. We aimed to determine the antimicrobial susceptibility and virulence factors for K. pneumoniae isolated from patients with bacteraemia or urinary tract infection (UTI) from 1999 to 2022. A total of 699 and 1,267 K. pneumoniae isolates were isolated from bacteraemia and UTI patients, respectively, and their susceptibility to twenty antibiotics was determined; PCR was used to identify capsular serotypes and virulence-associated genes. K64 and K1 serotypes were most frequently observed in UTI and bacteraemia, respectively, with an increasing frequency of K20, K47, and K64 observed in recent years. entB and wabG predominated across all isolates and serotypes; the least frequent virulence gene was htrA. Most isolates were susceptible to carbapenems, amikacin, tigecycline, and colistin, with the exception of K20, K47, and K64 where resistance was widespread. The highest average number of virulence genes was observed in K1, followed by K2, K20, and K5 isolates, which suggest their contribution to the high virulence of K1. In conclusion, we found that the distribution of antimicrobial susceptibility, virulence gene profiles, and capsular types of K. pneumoniae over two decades were associated with their clinical source.

Characterization of uropathogenic Escherichia coli phylogroups associated with antimicrobial resistance, virulence factor distribution, and virulence-related phenotypes.

In this study, we compared the characteristics of different uropathogenic Escherichia coli phylogroups. A total of 844 E. coli isolated from urine were enrolled and the antimicrobial susceptibility of E. coli to 22 antibiotics was determined by disk diffusion test. The distribution of phylogroups and 20 virulence factor genes was determined by PCR. Phenotypes associated with bacterial virulence, including motility, biofilm formation, and the production of curli and siderophore, were examined. Phylogroup B2 was dominant in our isolates (64.8%), followed by phylogroups D (8.6%), B1 (7.8%), F (6.0%), C (4.5%), A (3.1%), untypable (2.8%), E (1.8%), and clade I (0.5%). The prevalence of multidrug-resistant strains was highest in phylogroup C (86.8%), followed by E (80.0%), F (75.0%), and D (71.2%). Moreover, 23.5% of the phylogroup F E. coli were extensively drug-resistant. Phylogroup B2 E. coli had an average of the highest virulence factor genes (10.1 genes/isolate). Compared to phylogroup B2 E. coli, phylogroups F and clade I E. coli had higher motility while phylogroup C E. coli had lower motility. >60% of phylogroups A and C E. coli showed very low curli production. In contrast, 14%, 10%, and 7%, of E. coli in phylogroups F, B2, and E, produced a very high amount of curli, respectively. Surprisingly, phylogroup A E. coli showed the highest virulence to larvae, followed by phylogroups B2 and C. In summary, we first characterized and revealed that the antimicrobial resistance, virulence gene distribution, motility, and curli production, were associated with in E. coli phylogroups.

Role of antidiabetic agents in type 2 diabetes patients with chronic kidney disease.

Insulin resistance is a condition in which the target tissues have a decreased response to insulin signaling, resulting in glucose uptake defect, and an increased blood sugar level. Pancreatic beta cells thus enhance insulin production to compensate. This situation may cause further beta cell dysfunction and failure, which can lead diabetes mellitus (DM). Insulin resistance is thus an important cause of the development of type 2 DM. Insulin resistance has also been found to have a strong relationship with cardiovascular disease and is common in chronic kidney disease (CKD) patients. The mechanisms of insulin resistance in CKD are complex and multifactorial. They include physical inactivity, inflammation and oxidative stress, metabolic acidosis, vitamin D deficiency, adipose tissue dysfunction, uremic toxins, and renin-angiotensin-aldosterone system activation. Currently, available anti-diabetic agents, such as biguanides, sulfonylureas, thiazolidinediones, alfa-glucosidase inhibitors, glucagon-like peptide-1-based agents, and sodium-glucose co-transporter-2 inhibitors, have different effects on insulin resistance. In this short review, we describe the potential mechanisms of insulin resistance in CKD patients. We also review the interaction of currently available anti-diabetic medications with insulin resistance.

Characterization of host and escherichia coli strains causing recurrent urinary tract infections based on molecular typing.

BACKGROUND: Escherichia coli is the leading pathogen responsible for urinary tract infection (UTI) and recurrent UTI (RUTI). Few studies have dealt with the characterization of host and bacteria in RUTI caused by E. coli with genetically identical or different strains. This study aimed to investigate the host and bacterial characteristics of E. coli RUTI based on molecular typing. RESULTS: Patients aged 20 years or above who presented with symptoms of UTI in emergency department or outpatient clinics between August 2009 and December 2010 were enrolled. RUTI was defined as patients had 2 or more infections in 6 months or 3 or more in 12 months during the study period. Host factors (including age, gender, anatomical/functional defect, and immune dysfunction) and bacterial factors (including phylogenicity, virulence genes, and antimicrobial resistance) were included for analysis. There were 41 patients (41%) with 91 episodes of E. coli RUTI with highly related PFGE (HRPFGE) pattern (pattern similarity > 85%) and 58 (59%) patients with 137 episodes of E. coli RUTI with different molecular typing (DMT) pattern, respectively. There was a higher prevalence of phylogenetic group B2 and neuA and usp genes in HRPFGE group if the first episode of RUTI caused by HRPFGE E. coli strains and all episodes of RUTI caused by DMT E. coli strains were included for comparison. The uropathogenic E. coli (UPEC) strains in RUTI were more virulent in female gender, age < 20 years, neither anatomical/ functional defect nor immune dysfunction, and phylogenetic group B2. There were correlations among prior antibiotic therapy within 3 months and subsequent antimicrobial resistance in HRPFGE E. coli RUTI. The use of fluoroquinolones was more likely associated with subsequent antimicrobial resistance in most types of antibiotics. CONCLUSIONS: This study demonstrated that the uropathogens in RUTI were more virulent in genetically highly-related E. coli strains. Higher bacterial virulence in young age group (< 20 years) and patients with neither anatomical/functional defect nor immune dysfunction suggests that virulent UPEC strains are needed for the development of RUTI in healthy populations. Prior antibiotic therapy, especially the fluoroquinolones, within 3 months could induce subsequent antimicrobial resistance in genetically highly-related E. coli RUTI.

Machine learning to predict the development of recurrent urinary tract infection related to single uropathogen, Escherichia coli.

Recurrent urinary tract infection (RUTI) can damage renal function and has impact on healthcare costs and patients' quality of life. There were 2 stages for development of prediction models for RUTI. The first stage was a scenario in the clinical visit. The second stage was a scenario after hospitalization for urinary tract infection caused by Escherichia coli. Three machine learning models, logistic regression (LR), decision tree (DT), and random forest (RF) were built for the RUTI prediction. The RF model had higher prediction accuracy than LR and DT (0.700, 0.604, and 0.654 in stage 1, respectively; 0.709, 0.604, and 0.635 in stage 2, respectively). The decision rules constructed by the DT model could provide high classification accuracy (up to 0.92 in stage 1 and 0.94 in stage 2) in certain subgroup patients in different scenarios. In conclusion, this study provided validated machine learning models and RF could provide a better accuracy in predicting the development of single uropathogen (E. coli) RUTI. Both host and bacterial characteristics made important contribution to the development of RUTI in the prediction models in the 2 clinical scenarios, respectively. Based on the results, physicians could take action to prevent the development of RUTI.

Plasmid-mediated quinolone resistance determinants in fluoroquinolone-nonsusceptible Escherichia coli isolated from patients with urinary tract infections in a university hospital, 2009-2010 and 2020.

OBJECTIVES: This study aimed to characterize the plasmid-mediated quinolone resistance (PMQR) in fluoroquinolone nonsusceptible E. coli (FQNSEC) isolated from patients with urinary tract infections (UTIs) in 2019-2010 and 2020. METHODS: A total of 844 E. coli isolates were collected from UTI patients at National Cheng Kung University Hospital. The antimicrobial susceptibility of E. coli isolates to 21 antibiotics was determined by disk diffusion tests. The distribution of phylogenetic groups, virulence factor, and PMQR genes was determined by PCR. Conjugation assays were performed to investigate the transferability of qnr genes from FQNSEC isolates to E. coli C600. RESULTS: We found 211 (41.9%) and 152 (44.7%) E. coli isolates were FQNSEC in 2009-2010 and 2020, respectively. Phylogenetic group B2 was dominant in FQNSEC isolates (52.34%), followed by group F (10.47%), group B1 (9.64%), and group D (9.64%). FQNSEC isolates were more resistant to 17 of 19 tested antimicrobial agents, compared to the fluoroquinolone susceptible E. coli. PMQR screening results showed 34, 22, and 10 FQNSEC isolates containing aac(6')-Ib-cr, qnr genes, and efflux pump genes (qepA or oqxAB), respectively. PMQR E. coli isolates were more nonsusceptible to gentamicin, amoxicillin, ampicillin/sulbactam, imipenem, cefazolin, cefuroxime, cefmetazole, ceftriaxone, ceftazidime, and cefepime compared to non-PMQR FQNSEC. Moreover, 16 of 22 qnr-carrying plasmids were transferrable to the recipient C600. CONCLUSION: Here, we reported the high prevalence of MDR- and XDR-E. coli in FQNSEC isolates. Moreover, qnr-carrying plasmids were highly transferable and led to the resistance to other classes of antibiotics in the transconjugants.

Whole-genome-sequence-based characterization of an NDM-5-producing uropathogenic Escherichia coli EC1390.

BACKGROUND: Urinary tract infection (UTI) is one of the most common outpatient bacterial infections. In this study, we isolated and characterized an extensively-drug resistant (XDR) NDM-5-producing Escherichia coli EC1390 from a UTI patient by using whole-genome sequencing (WGS) in combination with phenotypic assays. METHODS: Antimicrobial susceptibility to 23 drugs was determined by disk diffusion method. The genome sequence of EC1390 was determined by Nanopore MinION MK1C platform. Conjugation assays were performed to test the transferability of EC1390 plasmids to E. coli recipient C600. Phenotypic assays, including growth curve, biofilm formation, iron acquisition ability, and cell adhesion, were performed to characterize the function of EC1390 plasmids. RESULTS: Our results showed that EC1390 was only susceptible to tigecycline and colistin, and thus was classified as XDR E. coli. A de novo genome assembly was generated using Nanopore 73,050 reads with an N50 value of 20,936 bp and an N90 value of 7,624 bp. WGS analysis showed that EC1390 belonged to the O101-H10 serotype and phylogenetic group A E. coli. Moreover, EC1390 contained 2 conjugative plasmids with a replicon IncFIA (pEC1390-1 with 156,286 bp) and IncFII (pEC1390-2 with 71,840 bp), respectively. No significant difference was observed in the bacterial growth rate in LB broth and iron acquisition ability between C600, C600 containing pEC1390-1, C600 containing pEC1390-2, and C600 containing pEC1390-1 and pEC1390-2. However, the bacterial growth rate in nutrition-limited M9 broth was increased in C600 containing pEC1390-2, and the cell adhesion ability was increased in C600 containing both pEC1390-1 and pEC1390-2. Moreover, these plasmids modulated the biofilm formation under different conditions. CONCLUSIONS: In summary, we characterized the genome of XDR-E. coli EC1390 and identified two plasmids contributing to the antimicrobial resistance, growth of bacteria in a nutrition-limited medium, biofilm formation, and cell adhesion.

Uremic Toxin-Producing Bacteroides Species Prevail in the Gut Microbiota of Taiwanese CKD Patients: An Analysis Using the New Taiwan Microbiome Baseline.

Rationale and Objective: Gut microbiota have been targeted by alternative therapies for non-communicable diseases. We examined the gut microbiota of a healthy Taiwanese population, identified various bacterial drivers in different demographics, and compared them with dialysis patients to associate kidney disease progression with changes in gut microbiota. Study Design: This was a cross-sectional cohort study. Settings and Participants: Fecal samples were obtained from 119 healthy Taiwanese volunteers, and 16S rRNA sequencing was done on the V3-V4 regions to identify the bacterial enterotypes. Twenty-six samples from the above cohort were compared with fecal samples from 22 peritoneal dialysis and 16 hemodialysis patients to identify species-level bacterial biomarkers in the dysbiotic gut of chronic kidney disease (CKD) patients. Results: Specific bacterial species were identified pertaining to different demographics such as gender, age, BMI, physical activity, and sleeping habits. Dialysis patients had a significant difference in gut microbiome composition compared to healthy controls. The most abundant genus identified in CKD patients was Bacteroides, and at the species level hemodialysis patients showed significant abundance in B. ovatus, B. caccae, B. uniformis, and peritoneal dialysis patients showed higher abundance in Blautia producta (p ≤ 0.05) than the control group. Pathways pertaining to the production of uremic toxins were enriched in CKD patients. The abundance of the bacterial species depended on the type of dialysis treatment. Conclusion: This study characterizes the healthy gut microbiome of a Taiwanese population in terms of various demographics. In a case-control examination, the results showed the alteration in gut microbiota in CKD patients corresponding to different dialysis treatments. Also, this study identified the bacterial species abundant in CKD patients and their possible role in complicating the patients' condition.

A Longitudinal Nine-Year Study of the Molecular Epidemiology of Carbapenemase-Producing Enterobacterales Isolated From a Regional Hospital in Taiwan: Predominance of Carbapenemase KPC-2 and OXA-48.

Enterobacterales clinical isolates are now being resistant to clinically achievable concentrations of most commonly used antibiotics that makes treatment of hospitalized patients very challenging. We hereby determine the molecular characteristics of carbapenemase genes in carbapenem-resistant Enterobacterales (CRE) isolates in Taiwan. A total of 455 CRE isolates were identified between August 2011 to July 2020. Minimum inhibitory concentrations for selected carbapenems were tested using Vitek 2, and carbapenemase genes were determined using polymerase chain reaction in combination with sequencing. Phenotypic detection of carbapenemase was determined by modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM) to validate our PCR screening results. Pulsed-field gel electrophoresis (PFGE) was used to determine the clonality of carbapenemase-producing Enterobacterales (CPE) isolates, and the transferability of carbapenemase-carrying plasmids was determined by conjugation assays. A slight increase in carbapenem-resistant E. coli (CREC) was observed, however, the prevalence of carbapenem-resistant K. pneumoniae (CRKP) was steady, during 2011-2020. The dominant species among our CRE was K. pneumoniae (270/455, 59.3%), followed by E. coli (81/455, 17.8%), Morganella morganii (32/455, 7.0%), and Enterobacter cloacae (25/455, 5.5%). From 2011 to 2020, the total percentage of CPE increased steadily, accounting for 61.0% of CRE in 2020. Moreover, 122 of 455 CRE isolates (26.8%) were CPE. Among the CPE isolates, the dominant carbapenemase gene was bla OXA-48-like (54/122, 44.3%), and the second most common carbapenemase gene was bla KPC-2 (47/122, 38.5%). The sensitivity and specificity for mCIM to detect carbapenemase in the 455 isolates were both 100% in this study. The PFGE results showed that 39 carbapenemase-producing E. coli and 69 carbapenemase-producing K. pneumoniae isolates carrying bla KPC-2 and/or bla NDM-5 could be classified into 5 and 12 clusters, respectively. In conclusion, our results showed an increase in CPE isolates in Taiwan. Moreover, the distribution of carbapenemase and antimicrobial susceptibility in CPE were associated with PFGE typing.

Association of retinopathy severity with cardiovascular and renal outcomes in patients with type 1 diabetes: a multi-state modeling analysis.

This study aimed to assess the impact of diabetic retinopathy (DR) severity on the incidence of major adverse cardiac events (MACE) and end-stage renal disease (ESRD) in T1D patients. Patients diagnosed with T1D between 1999 and 2013 were identified from patient-level data of Taiwan's National Health Insurance Research database. A total of 1135 patients were included and classified into mild DR (n = 454), severe DR (n = 227), or non-DR (n = 454) by using propensity score matching. Multi-state model analyses, an extension of competing risk models with adjustment for transition-specific covariates for prediction of subsequent MACE and ESRD, were performed. MACE and ESRD risks were significantly higher in the severe DR patients; a 2.97-fold (1.73, 5.07) and 12.29-fold (6.50, 23.23) increase in the MACE risk among the severe DR patients compared to the mild DR and DR-free patients, respectively; and, a 5.91-fold (3.50, 9.99) and 82.31-fold (29.07, 233.04) greater ESRD risk of severe DR patients than that of the mild DR and DR-free groups, respectively (p < 0.001). Severity of DR was significantly associated with the late diabetes-related vascular events (i.e., MACE, ESRD) among T1D patients.

Association between Escherichia coli with NotI-restriction resistance and urinary tract infections.

BACKGROUND: Escherichia coli is the most common cause of urinary tract infections (UTIs). It is widely accepted that uropathogenic E. coli (UPEC) mainly emerge from the distal gut microbiota. Identification of bacterial characteristics that are able to differentiate UPEC from fecal commensal strains will facilitate the development of novel strategies to detect and monitor the spread of UPEC. METHODS: Fifty fecal commensal, 83 UTI-associated and 40 biliary tract infection (BTI)-associated E. coli isolates were analyzed. The NotI restriction patterns of chromosomal DNA in the isolates were determined by pulse-field gel electrophoresis. The phylogenetic types and the presence of 9 known virulence genes of each isolate were determined by PCR analyses. Additionally, the susceptibilities of the isolates to antibiotics were revealed. Then the associations of NotI resistance with UTI-associated isolates, phylotypes, and antibiotic resistance were assessed. RESULTS: NotI resistance was correlated with UTI-associated isolates, compared to the fecal isolates. Consistently, NotI-resistant isolates harbored a greater number of virulence factors and mainly belonged to phylotype B2. Additionally NotI resistance was correlated with chloramphenicol resistance among the bacteria. Among the fecal, UTI-associated and BTI-associated groups, the distribution of NotI-resistant group B2 isolates was correlated with UTI-associated bacteria. CONCLUSION: NotI resistance alone is a potential marker for distinguishing fecal strains and UPEC, while the combination of NotI resistance and B2 phylogeny is a candidate marker to differentiate UPEC from fecal and other extraintestinal pathogenic E. coli. Additionally, NotI resistance may be valuable for assessing the potential of chloramphenicol resistance of E. coli.

Escherichia coli FimH adhesins act synergistically with PapGII adhesins for enhancing establishment and maintenance of kidney infection.

BACKGROUND: FimH adhesin is proposed to enhance Escherichia coli kidney infection by acting with PapGII adhesin, but genetic epidemiology study and animal study have not been widely conducted to confirm this hypothesis. METHODS: We compared the prevalence of adhesin gene and their coexistent pattern between upper and lower urinary tract infection (UTI) strains. fimH mutant (EC114FM), papGII mutant (EC114PM) and fimH/papGII double mutant (EC114DM) were constructed from a pylonephritogenic strain (EC114). We compared among these strains for the infection ability in bladders and kidneys of female BALB/c mice challenged transurethrally with these bacteria and assessed 1, 3, and 7 days after inoculation. RESULTS: Strains carrying fimH-only genotype were significantly more prevalent in lower UTI (P < 0.001). Strains carrying the fimH/papGII, but not papGII-only, were significantly associated with upper UTI (P = 0.001). Incidence of kidney infection increased after inoculation with EC114 on days 1 and 3, at both low and high dose, as compared with EC114DM; and the effect was greater than the sum of individual effect of EC114PM and EC114FM. Geometric means of quantitative bacterial counts in the kidneys significantly decreased when challenged with EC114FM on days 3 and 7, EC114PM on day 3 and EC114DM on day 1 after inoculation at high dose, as compared with EC114 (all P < 0.05). CONCLUSIONS: We confirmed the advantage and synergistic action of FimH and PapGII for E. coli kidney infection and concluded that antagonists against FimH and PapGII adhesin may prevent kidney infection and enable its management.

Escherichia coli urinary tract infections: Host age-related differences in bacterial virulence factors and antimicrobial susceptibility.

BACKGROUND: Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are one of the most common outpatient bacterial infections. Although bacterial and host factors are reported to be associated with UTI pathogenesis, little is known about the host age-related differences in bacterial virulence factors and antimicrobial susceptibility. METHODS: PCRs were carried out to detect K1 capsule antigen, 15 virulence factors, and phylogenetic groups in E. coli isolates. Antimicrobial susceptibility of selected agents was determined by the disk diffusion method. Isolates were divided into 6 groups based on their host age. RESULTS: The results showed that virulence factors PapGII, PapGIII, Cnf1, Aer, Usp, Iha, OmpT, HlyA, and Sat, had highest frequencies in the host age group 0-3. Phylogenetic group B2 dominated in our isolates (59.6%) followed by group D (20.7%). In addition, 77.4% of strains isolated from 0 to 3 age group belonged to phylogenetic group B2. Antimicrobial susceptibility tests showed that E. coli strains isolated were significantly more resistant to antimicrobial agents as host age increased. Phylogenetic group B2 isolates were more susceptible to antimicrobial agents, compared to A, B1, and D isolates. CONCLUSION: We found E. coli isolated from elders were more resistant to antimicrobial agents and had less virulence factors.

Ureteral stone with hydronephrosis and urolithiasis alone are risk factors for acute kidney injury in patients with urinary tract infection.

To identify whether urolithiasis with or without hydronephrosis has an impact on acute kidney injury (AKI) in patients with urinary tract infection (UTI). This study aimed to identify whether urolithiasis with or without hydronephrosis has an impact on AKI in patients with UTI. This retrospective study enrolled hospitalized UTI patients who underwent imaging in an acute care setting from January 2006 to April 2019. Of the 1113 participants enrolled, 191 (17.2%) had urolithiasis and 76 (6.8%) had ureteral stone complicated with hydronephrosis. Multivariate logistic regression analysis showed that in UTI patients with urolithiasis, the presence of ureteral stone with concomitant hydronephrosis was an independent risk factor for AKI (odds ratio [OR] 2.299, 95% confidence interval [CI] 1.112-4.755, P = 0.025). In addition, urolithiasis was associated with an increased risk for AKI (OR 2.451, 95% CI 1.369-4.389, P = 0.003) in UTI patients without hydronephrosis. The presence of ureteral stone with hydronephrosis increases the risk for AKI of UTI patients with urolithiasis, and urolithiasis remains a risk factor of AKI in UTI patients without hydronephrosis.