Human Urinary Tract Research Articles

Virulence potential of antimicrobial-resistant extraintestinal pathogenic Escherichia coli from retail poultry meat in a Caenorhabditis elegans model

Healthy poultry can be a reservoir for extraintestinal pathogenic Escherichia coli (ExPEC), some of which could be multidrug resistant to antimicrobials. These ExPEC strains could contaminate the environment and/or food chain representing thus, food safety and human health risk. However, few studies have shown the virulence of poultry-source antimicrobial-resistant (AMR) ExPEC in humans. This study characterized AMR ExPEC and investigated the virulence potential of some of their isolates in a Caenorhabditis elegans infection model. A total of 46 E. coli isolates from poultry (chicken, n = 29; turkey, n = 12) retail meats and chicken feces (n = 4), or humans (n = 1) were sequenced and identified as ExPEC. Except eight, all remaining 38 ExPEC isolates were resistant to at least one antibiotic and carried corresponding antimicrobial resistance genes (ARGs). About 27 of the 46 ExPEC isolates were multidrug-resistant (≥3 antibiotic classes). Seven ExPEC isolates from chicken or turkey meats were of serotype O25:H4 and sequence type (ST) 131 which clustered with an isolate from a human urinary tract infection (UTI) case having the same serotype and ST. The C. elegans challenge model using eight of studied ExPEC isolates harboring various ARGs and virulence genes (VGs) showed that regardless of their ARG or VG numbers in tested poultry meat and feces, ExPEC significantly reduced the life span of the nematode (P < 0.05) similarly to a human UTI isolate. This study indicated the pathogenic potential of AMR ExPEC from retail poultry meat or feces, but more studies are warranted to establish their virulence in poultry and human. Furthermore, relationships between specific resistance profiles and/or VGs in these E. coli isolates for their pathogenicity deserve investigations.

Expression and distribution of the transient receptor potential cationic channel ankyrin 1 (TRPA1) in the human seminal vesicles.

The transient receptor potential cationic channel ankyrin 1 (TRPA1), a channel protein permeable to most divalent cations, has been suggested to play a role in mechano-afferent/efferent signaling (including the release of neurotransmitters) in the human urinary tract (bladder, prostate, and urethra). To date, only a few studies have addressed the expression of this receptor in male and female reproductive tissues. The present study aimed to evaluate human seminal vesicles (SVs) for the expression and localization of TRPA1. SV tissue was obtained from 5 males who had undergone pelvic surgery due to malignancies of the prostate or urinary bladder. The expression of messenger ribonucleic acid (mRNA) specifically encoding for the TRPA1 protein was elucidated by means of reverse transcriptase polymerase chain reaction (RT-PCR). Using immunohistochemical methods, the distribution of TRPA1 was examined in relation to the endothelial and neuronal nitric oxide synthases (eNOS, nNOS) and the neuropeptides calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP). RT-PCR revealed signals related to the expected molecular size of 656 bp. Immunohistochemistry demonstrated that TRPA1 is located in nerves running through the smooth muscle portion of the SV. Here, the protein is in part co-localized with nNOS and CGRP, whereas no co-localization with VIP was registered. Dot-like signals specific for TRPA1 were observed in the cytoplasm of epithelial cells lining the lumen of glandular spaces. The epithelial layer also presented staining for eNOS. The smooth musculature appeared free of immunosignals for TRPA1. The results convincingly show the expression of TRPA1 in nerve endings as well as in epithelial cells of the SV. Based on its location in epithelial cells, TRPA1 might be involved in the mechanism of the NO/cyclic guanosine monophosphate (GMP)-mediated signaling and also the control of secretory function (mediated by cyclic GMP) in the human SV.

Prevalence of main quinolones and carbapenems resistance genes in clinical and veterinary Escherichia coli strains.

Antibiotics-resistant Escherichia coli strains are considered one of the most important causes of human and animal infections worldwide. The aim of current study was to detect common resistance (carbapenems and quinolones) genes by PCR. A total of 100 E. coli strains isolated from human urinary tract infection and 20 isolated strains of aborted sheep embryos were collected. PCR was performed using specific primers to detect the resistance genes. Overall, among the quinolones resistance genes, qnrS resistance gene had the highest frequency (48%) and among carbapenem resistance genes, imp resistance gene had the highest frequency (45%). The frequency of resistance genes, IMP (28.45%), KPC (9.5%), VIM (9.15%), NDM (7.20%) were observed in clinical and veterinary strains, respectively. According to the results, 38.6% of E. coli strains had at least one from five genes of resistance to quinolones. The lowest frequency of resistance gene was related to qnrA, which was observed in only 29 (24.2%) strains. Monitoring of carbapenem and quinolone resistance in pathogenic E. coli to humans and animals has an important value in revising treatment guidelines and the national public health, and plays an important role in preventing the spread of resistant strains.

A systematic review of the correlation between Trichomonas vaginalis infection and infertility

BackgroundTrichomonas vaginalis (T. vaginalis) is an extracellular flagellated protozoan parasitizing the human genital and urinary tracts. T. vaginalis infection impacts human reproductive function, but whether it causes infertility is still a matter of debate. MethodsIn this work, we consulted 205 relevant articles, which were classified into three categories: epidemiological investigations (100), review articles (43), and research articles (62). RevMan 5.4 was used to conduct a meta-analysis of the articles reporting epidemiological investigations comparing the incidence of T. vaginalis infection between infertile and fertile groups. Review and research articles were used to summarize the pathogenesis of infertility caused by T. vaginalis. ResultsThe results indicated that rate of T. vaginalis infection in the infertile group was significantly higher than that in the fertile group. Moreover, the epidemiological surveys showed that the infertility rates of population infected with T. vaginalis were significantly higher than that of population without T. vaginalis infection. Nine out of ten (90%) related review articles stated that T. vaginalis infection causes infertility, and the review and research articles indicated the main pathogenic mechanisms of infertility caused by T. vaginalis were as follows: T. vaginalis impairs sperm quality, resulting in infertility; the immune response triggered by T. vaginalis infection impacts human reproductive function. ConclusionOur results confirm that there is a correlation between T. vaginalis infection and infertility, and T. vaginalis infection can lead to infertility. The study provides a foundation for further investigations into its pathogenesis.

Phylotypic Profiling, Distribution of Pathogenicity Island Markers, and Antimicrobial Susceptibility of Escherichia coli Isolated from Retail Chicken Meat and Humans.

Escherichia coli (E.coli) found in retail chicken meat could be causing a wide range of infections in humans and constitute a potential risk. This study aimed to evaluate 60 E. coli isolates from retail chicken meat (n = 34) and human urinary tract infections (UTIs, n = 26) for phylogenetic diversity, presence of pathogenicity island (PAI) markers, antimicrobial susceptibility phenotypes, and antimicrobial resistance genes, and to evaluate their biofilm formation capacity. In that context, confirmed E.coli isolates were subjected to phylogrouping analysis using triplex PCR, antimicrobial susceptibility testing using the Kirby–Bauer disc diffusion method; PAI distribution was investigated by using two multiplex PCRs. Most of the chicken isolates (22/34, 64.7%) were identified as commensal E. coli (A and B1), while 12 isolates (35.3%) were classified as pathogenic virulent E. coli (B2 and D). Similarly, the commensal group dominated in human isolates. Overall, 23 PAIs were detected in the chicken isolates; among them, 39.1% (9/23) were assigned to group B1, 34.8% (8/23) to group A, 4.34% (1/23) to group B2, and 21.7% (5/23) to group D. However, 25 PAIs were identified from the human isolates. PAI IV536 was the most prevalent (55.9%, 69.2%) PAI detected in both sources. In total, 37 (61.7%) isolates of the chicken and human isolates were biofilm producers. Noticeably, 100% of E. coli isolates were resistant to penicillin and rifamycin. Markedly, all E. coli isolates displayed multiple antibiotic resistance (MAR) phenotypes, and the multiple antibiotic resistance index (MARI) among E. coli isolates ranged between 0.5 and 1. Several antibiotic resistance genes (ARGs) were identified by a PCR assay; the sul2 gene was the most prevalent (38/60, 63.3%) from both sources. Interestingly, a significant positive association (r = 0.31) between biofilm production and resistance to quinolones by the qnr gene was found by the correlation analysis. These findings were suggestive of the transmission of PAI markers and antibiotic resistance genes from poultry to humans or humans to humans through the food chain. To avoid the spread of virulent and multidrug-resistant E. coli, intensive surveillance of retail chicken meat markets is required.

Urinary Tract Infections Caused by Uropathogenic Escherichia coli Strains-New Strategies for an Old Pathogen.

Urinary tract infections (UTIs) are among the most common infections worldwide. Uropathogenic Escherichia coli (UPECs) are the main causative agent of UTIs. UPECs initially colonize the human host adhering to the bladder epithelium. Adhesion is followed by the bacterial invasion of urothelial epithelial cells where they can replicate to form compact aggregates of intracellular bacteria with biofilm-like properties. UPEC strains may persist within epithelial urothelial cells, thus acting as quiescent intracellular bacterial reservoirs (QIRs). It has been proposed that host cell invasion may facilitate both the establishment and persistence of UPECs within the human urinary tract. UPEC strains express a variety of virulence factors including fimbrial and afimbrial adhesins, invasins, iron-acquisition systems, and toxins, which cooperate to the establishment of long lasting infections. An increasing resistance rate relative to the antibiotics recommended by current guidelines for the treatment of UTIs and an increasing number of multidrug resistant UPEC isolates were observed. In order to ameliorate the cure rate and improve the outcomes of patients, appropriate therapy founded on new strategies, as alternative to antibiotics, needs to be explored. Here, we take a snapshot of the current knowledge of coordinated efforts to develop innovative anti-infective strategies to control the diffusion of UPECs.

Highly selective and sensitive nitrite biocathode biosensor prepared by polarity inversion method coupled with selective removal of interfering electroactive bacteria

Nitrite is a multipurpose marker that needs to be detected quickly and accurately, including for water pollution and human urinary tract infections. In this study, we reported a novel nitrite-reducing bacteria electrochemical biosensor based on the metronidazole-treated biocathode (MT-NBEB). The biocathode with high nitrite response sensitivity used was first prepared by polarity inversion method and then treated with metronidazole to selectively remove the interfering electroactive bacteria for selectivity improvement. MT-NBEB could detect nitrite in the range of 0.0001 mg NO2−-N L−1–8 mg NO2−-N L−1 within 1.7 min and maintain stable detection performance for over 50 continuous cycles with relative standard deviations < 2.4%. Besides, the response signals of MT-NBEB were not affected by the common inorganic salts (such as nitrate and ammonia) and organic matter (such as acetate). MT-NBEB successfully detected nitrite in five types of wastewaters with relative errors < 14.3%. Our study provided a feasible way to prepare highly selective and sensitive electrochemical biosensors to quickly and accurately detect nitrite in real wastewaters.

Comparative Characteristics and Pathogenic Potential of Escherichia coli Isolates Originating from Poultry Farms, Retail Meat, and Human Urinary Tract Infection.

The pathogenicity of many bacterial strains is determined by the acquisition of virulence genes and depends on many factors. The aim of this study was to analyse the phylogenetic background, virulence patterns, and drug susceptibility of 132 E. coli isolates tested in the context of the ExPEC (Extraintestinal Pathogenic E. coli) pathotype and the correlation of these features with bacterial isolation source: food (retail meat), poultry farms (AFEC—Avian Faecal E. coli), and patients with UTI (urinary tract infection) symptoms. The drug-susceptibility results of tested E. coli isolates obtained indicate that the resistance profile—ampicillin/tetracycline/trimethoprim+sulfamethoxazole/ciprofloxacin (AMP/TE/SXT/CIP)—was most frequently observed. The multidrug resistance (MDR) phenotype was found in 31.8% of isolates from poultry farms, 36.8% of strains isolated from food, and 20% of clinical samples. The greatest similarity of virulence profiles applied to isolates derived from poultry farms and food. Most of the AFEC from poultry farms and food-derived isolates belonged to commensals from phylogroups A and B1, while among the isolates from patients with UTI symptoms, the most common was the B2 phylogroup. The collective analysis showed similarity of the three studied groups of E. coli isolates in terms of the presented patterns of antimicrobial resistance, while the virulence profiles of the isolates studied showed great diversity. The phylogroup analysis showed no similarity between the poultry/food isolates and the UTI isolates, which had significant pathogenic potential.

Virulence potential of the first Corynebacterium mycetoides strain isolated from human urine: a rare species of Corynebacterium

For many years, the potential pathogenic of non-diphtheriae corynebacteria were underestimated. Nowadays, a growing number of Corynebacterium species are recognized as opportunistic agents of human infections, mainly in hospital settings. In addition, multidrug-resistant Corynebacterium isolates from clinical specimens, have been reported and the role of Corynebacterium spp. in urinary tract infections (UTIs) has been highlighted. Several studies have reported Corynebacterium species as the agent of UTIs especially in patients with risk factors. Thus, the present work aimed to report the first isolation of Corynebacterium mycetoides from human urine and an initial study on its virulence properties. The isolate, initially characterized by phenotypical tests as a multidrug-resistant Corynebacterium sp., was recovered from the urine of a female transplant patient. Mass spectrometry and 16S rRNA and rpoB genes sequencing identified the isolate as C. mycetoides. The isolate was found able to adhere to and survive into epithelial cells (Vero cells), and its pathogenic potential was confirmed when tested against Caenorhabditis elegans nematode. The results obtained suggest that C. mycetoides is a potential pathogen for the urinary tract in humans and for a better understanding of the multifactorial mechanisms of virulence, studies about this species should be continued.

Uropathogenic Escherichia coli can cause cystitis at extremely low inocula in a pig model.

Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. Experimental models that accurately reflect the high susceptibility to UTI in humans have, however, been lacking. This situation has limited detailed research into the early bladder colonization by uropathogens and the early innate defence mechanisms elicited to prevent this. We recently presented a model of urinary tract infection in pigs, animals that are naturally susceptible to UTI and have greater similarity to the physiology and anatomy of the human urinary tract than traditional rodent UTI models. In the current study, we used the pig model to investigate the minimal infectious inoculum of uropathogenic Escherichia coli, the most common cause of urinary tract infection. We show that in this animal a few individual bacteria that come into contact with the urothelium can give rise to fulminant cystitis, indicating the high infectious potential of uropathogenic E. coli.

Multidrug-Resistant Klebsiella variicola Isolated in the Urine of Healthy Bovine Heifers, a Potential Risk as an Emerging Human Pathogen.

Klebsiella variicola, a member of Klebsiella pneumoniae complex, is found to infect plants, insects, and animals and is considered an emerging pathogen in humans. While antibiotic resistance is often prevalent among K. variicola isolates from humans, this has not been thoroughly investigated in isolates from nonhuman sources. Prior evidence suggests that K. variicola can be transmitted between agricultural products as well as between animals, and the use of antibiotics in agriculture has increased antibiotic resistance in other emerging pathogens. Furthermore, in animals that contain K. variicola as a normal member of the rumen microbiota, the same bacteria can also cause infections, such as clinical mastitis in dairy cows. Here, we describe K. variicola UFMG-H9 and UFMG-H10, both isolated from the urine of healthy Gyr heifers. These two genomes represent the first isolates from the urine of cattle and exhibit greater similarity with strains from the human urinary tract than isolates from bovine fecal or milk samples. Unique to the UFMG-H9 genome is the presence of flagellar genes, the first such observation for K. variicola. Neither of the sampled animals had symptoms associated with K. variicola infection, even though genes associated with virulence and antibiotic resistance were identified in both strains. Both strains were resistant to amoxicillin, erythromycin, and vancomycin, and UFMG-H10 is resistant to fosfomycin. The observed resistances emphasize the concern regarding the emergence of this species as a human pathogen given its circulation in healthy livestock animals. IMPORTANCE Klebsiella variicola is an opportunistic pathogen in humans. It also has been associated with bovine mastitis, which can have significant economic effects. While numerous isolates have been sequenced from human infections, only 12 have been sequenced from cattle (fecal and milk samples) to date. Recently, we discovered the presence of K. variicola in the urine of two healthy heifers, the first identification of K. variicola in the bovine urinary tract and the first confirmed K. variicola isolate encoding for flagella-mediated motility. Here, we present the genome sequences and analysis of these isolates. The bovine urinary genomes are more similar to isolates from the human urinary tract than they are to other isolates from cattle, suggesting niche specialization. The presence of antibiotic resistance genes is concerning, as prior studies have found transmission between animals. These findings are important to understand the circulation of K. variicola in healthy livestock animals.

GC/MS Analysis and In vitro Effect of Ganoderma lucidum Solvent Extracts on Microorganisms Isolated from the Armpit, Scalp and Urinary Tract

Aims: The study was to assess the antibacterial effect of solvent extracts of Ganoderma lucidum on isolates from the human scalp, armpit, and urinary tract.&#x0D; Study Design: Descriptive comparative.&#x0D; Place and Duration of Study: the Bells University of Technology, between December 2019 and October 2020.&#x0D; Methodology: Test organisms isolated from the scalp, armpit, and urine were identified using conventional methods and Analytical Profile Index kits (API). Ganoderma lucidum was rinsed with 2.5% potassium hydroxide and sterile distilled water, dried at 50℃ for 72 h, and pulverized. The mushroom powder (10%) was extracted in methanol, acetone, and petroleum ether at 65oC for 48 h. The filtrate was evaporated and two-fold serial dilutions were prepared in Dimethyl sulfoxide (DMSO). Antibacterial activity was done by the agar well diffusion method. Inoculum adjusted to 0.5 McFarland standard was inoculated onto Mueller Hinton agar. Wells of 6mm were filled with 100ml of the extracts. Antibiotic sensitivity was by disc diffusion method. Plates were incubated at 37oC for 24 h. Gas chromatography-mass spectrophotometer (GC-MC) analysis of methanol extract was carried out.&#x0D; Results: The isolates were identified as follows; scalp (Corynebacterium kutscheri and Enterobacter intermedius), armpit (Acinetobacter baumannii), and urine (Pseudomonas aeruginosa). The solvents exhibited varying degrees of inhibition on test organisms. The methanol extract was most inhibitory on all organisms. Petroleum ether showed the least inhibition. P. aeruginosa was most resistant to the extracts. Fluoroquinolones and aminoglycosides inhibited all the organisms and recorded a higher zone of inhibition, unlike the beta-lactams. GC/MS of methanol extract revealed the presence of 48 compounds amongst them were sugar, alcohols, nitrates, alkaloids, amines, fatty acids, methyl esters, and steroids. Also found was Phenol, 2-methoxy butylated hydroxyl anisole (BHA) an antioxidant.&#x0D; Conclusion: Ganoderma lucidum contained bioactive compounds that are antimicrobial and showed utility for use in the medical-pharmaceutical industry.

Multi-Modal X-ray Imaging and Analysis for Characterization of Urinary Stones

Backgound: The composition of stones formed in the urinary tract plays an important role in their management over time. The most common imaging method for the non-invasive evaluation of urinary stones is radiography and computed tomography (CT). However, CT is not very sensitive, and cannot differentiate between all critical stone types. In this study, we propose the application, and evaluate the potential, of a multi-modal (or multi-contrast) X-ray imaging technique called speckle-based imaging (SBI) to differentiate between various types of urinary stones. Methods: Three different stone samples were extracted from animal and human urinary tracts and examined in a laboratory-based speckle tracking setup. The results were discussed based on an X-ray diffraction analysis and a comparison with X-ray microtomography and grating-based interferometry. Results: The stones were classified through compositional analysis by X-ray diffraction. The multi-contrast images obtained using the SBI method provided detailed information about the composition of various urinary stone types, and could differentiate between them. X-ray SBI could provide highly sensitive and high-resolution characterizations of different urinary stones in the radiography mode, comparable to those by grating interferometry. Conclusions: This investigation demonstrated the capability of the SBI technique for the non-invasive classification of urinary stones through radiography in a simple and cost-effective laboratory setting. This opens the possibility for further studies concerning full-field in vivo SBI for the clinical imaging of urinary stones.

Regulation of Escherichia coli fim gene transcription by GadE and other acid tolerance gene products.

Uropathogenic Escherichia coli (UPEC) cause millions of urinary tract infections each year in the United States. Type 1 pili are important for adherence of UPEC to uroepithelial cells in the human and murine urinary tracts where osmolality and pH vary. Previous work has shown that an acidic pH adversely affects the expression of type 1 pili. To determine if acid tolerance gene products may be regulating E. coli fim gene expression, a bank of K-12 strain acid tolerance gene mutants were screened using fimA-lux, fimB-lux, and fimE-lux fusions on single copy number plasmids. We have determined that a mutation in gadE increased transcription of all three fim genes, suggesting that GadE may be acting as a repressor in a low pH environment. Complementation of the gadE mutation restored fim gene transcription to wild-type levels. Moreover, mutations in gadX, gadW, crp, and cya also affected transcription of the three fim genes. To verify the role GadE plays in type 1 pilus expression, the NU149 gadE UPEC strain was tested. The gadE mutant had higher fimE gene transcript levels, a higher frequency of Phase-OFF positioning of fimS, and hemagglutination titres that were lower in strain NU149 gadE cultured in low pH medium as compared to the wild-type bacteria. The data demonstrate that UPEC fim genes are regulated directly or indirectly by the GadE protein and this could have some future bearing on the ability to prevent urinary tract infections by acidifying the urine and shutting off fim gene expression.

Virulome and genome analyses identify associations between antimicrobial resistance genes and virulence factors in highly drug-resistant Escherichia coli isolated from veal calves.

Food animals are known reservoirs of multidrug-resistant (MDR) Escherichia coli, but information regarding the factors influencing colonization by these organisms is lacking. Here we report the genomic analysis of 66 MDR E. coli isolates from non-redundant veal calf fecal samples. Genes conferring resistance to aminoglycosides, β-lactams, sulfonamides, and tetracyclines were the most frequent antimicrobial resistance genes (ARGs) detected and included those that confer resistance to clinically significant antibiotics (blaCMY-2, blaCTX-M, mph(A), erm(B), aac(6’)Ib-cr, and qnrS1). Co-occurrence analyses indicated that multiple ARGs significantly co-occurred with each other, and with metal and biocide resistance genes (MRGs and BRGs). Genomic analysis also indicated that the MDR E. coli isolated from veal calves were highly diverse. The most frequently detected genotype was phylogroup A-ST Cplx 10. A high percentage of isolates (50%) were identified as sequence types that are the causative agents of extra-intestinal infections (ExPECs), such as ST69, ST410, ST117, ST88, ST617, ST648, ST10, ST58, and ST167, and an appreciable number of these isolates encoded virulence factors involved in the colonization and infection of the human urinary tract. There was a significant difference in the presence of multiple accessory virulence factors (VFs) between MDR and susceptible strains. VFs associated with enterohemorrhagic infections, such as stx, tir, and eae, were more likely to be harbored by antimicrobial-susceptible strains, while factors associated with extraintestinal infections such as the sit system, aerobactin, and pap fimbriae genes were more likely to be encoded in resistant strains. A comparative analysis of SNPs between strains indicated that several closely related strains were recovered from animals on different farms indicating the potential for resistant strains to circulate among farms. These results indicate that veal calves are a reservoir for a diverse group of MDR E. coli that harbor various resistance genes and virulence factors associated with human infections. Evidence of co-occurrence of ARGs with MRGs, BRGs, and iron-scavenging genes (sit and aerobactin) may lead to management strategies for reducing colonization of resistant bacteria in the calf gut.

Escherichia coli and Pseudomonas aeruginosa Isolated From Urine of Healthy Bovine Have Potential as Emerging Human and Bovine Pathogens.

The study of livestock microbiota has immediate benefits for animal health as well as mitigating food contamination and emerging pathogens. While prior research has indicated the gastrointestinal tract of cattle as the source for many zoonoses, including Shiga-toxin producing Escherichia coli and antibiotic resistant bacteria, the bovine urinary tract microbiota has yet to be thoroughly investigated. Here, we describe 5 E. coli and 4 Pseudomonas aeruginosa strains isolated from urine of dairy Gyr cattle. While both species are typically associated with urinary tract infections and mastitis, all of the animals sampled were healthy. The bovine urinary strains were compared to E. coli and P. aeruginosa isolates from other bovine samples as well as human urinary samples. While the bovine urinary E. coli isolates had genomic similarity to isolates from the gastrointestinal tract of cattle and other agricultural animals, the bovine urinary P. aeruginosa strains were most similar to human isolates suggesting niche adaptation rather than host adaptation. Examination of prophages harbored by these bovine isolates revealed similarity with prophages within distantly related E. coli and P. aeruginosa isolates from the human urinary tract. This suggests that related urinary phages may persist and/or be shared between mammals. Future studies of the bovine urinary microbiota are needed to ascertain if E. coli and P. aeruginosa are resident members of this niche and/or possible sources for emerging pathogens in humans.

Ex Vivo Near-Infrared Molecular Imaging of Human Upper Urinary Tract Urothelial Carcinoma With a CD47-Based Targeted Tracer.

ObjectiveThe low detection rate of early and small tumors remains a clinical problem that urgently needs to be solved in the accurate diagnosis and treatment of upper urinary tract urothelial carcinoma (UTUC). The objective of this study is to evaluate the feasibility of CD47 as a target for optical molecular imaging of human UTUC and conduct preliminary ex vivo imaging experiments.MethodsWe firstly analyzed the genome-wide mRNA expression data from Gene Expression Omnibus (GEO). Paraffin-embedded tissue specimens comprising UTUC and normal urothelium were collected. All tissue specimens were used for immunohistochemistry to compare CD47 protein expression in normal and cancer tissue. Meanwhile, 12 patients undergoing radical nephroureterectomy were prospectively included in ex vivo imaging experiments. Freshly isolated upper urinary tract specimens were incubated with anti-CD47-Alexa Fluor 790 and then imaged under white light and near-infrared (NIR) light. Standard histopathologic evaluation was performed, and findings were correlated with CD47-targeted NIR molecular imaging.ResultsThe GEO data revealed that CD47 mRNA expression was higher in UTUC specimens than that in paracancer normal tissue. In immunohistochemical analysis, the CD47 protein expression level was higher in both non-muscle-invasive and muscle-invasive (stage ≥T2) UTUCs than that in normal uroepithelium, and the localization of CD47 protein was the tumor cell membrane. In the ex vivo imaging experiments, all patients were pathologically diagnosed with UTUC, and no adverse effects of anti-CD47-Alexa Fluor 790 on the histological structure of the tumor and normal uroepithelium were observed. In the NIR grayscale images, the mean fluorescence intensity of the tumor tissue was significantly higher than that of the adjacent normal background tissue, which greatly improved the visualization of the tumor.ConclusionsCD47-targeted NIR molecular imaging could be a feasible and powerful strategy for the accurate diagnosis of UTUC. Larger-scale randomized trials are needed.

Comparison of the effectiveness of the antibiotics Fosfomycin and levofloxacin in acute cystitis: a systematic review and meta-analysis

Urinary tract infection or UTI is an infection caused by microorganisms that grow in the human urinary tract. Cystitis is a urinary tract infection (UTI) in the bladder (Li &amp; Lesli, 2018). According to the National Kidney and Urological Diseases Information Clearinghouse or NKUDIC, urinary tract infections are the second most common infectious disease after respiratory tract infections, and 8.3 million cases are reported annually. Urinary tract infections can affect patients ranging from new-borns to the elderly. The main treatment for urinary tract infections is treatment using antibiotics according to the 2015 Guidelines on Urological Infections of the European Association of Urology (EAU). Fosfomycin is the main therapy for the treatment of cystitis while levofloxacin is an alternative therapy. Fosfomycin is the main therapy for cystitis, but the drug that is commonly found on the market is levofloxacin. Purpose. This study aims to compare the effectiveness of the antibiotic Fosfomycin with levofloxacin in acute cystitis. method. This meta-analysis research uses various literature sourced from Cochrane, PubMed, Google Scholar, and ScienceDirect. A literature search using the keywords “Fosfomycin” and “levofloxacin” and “cystitis” and “acute”. This research uses the Review Manager 5.4 application. Results. Fosfomycin is more effective against E. coli bacteria, but levofloxacin is more effective against Fosfomycin on S. saprophyticus bacteria. E. coli bacteria are more resistant to levofloxacin than Fosfomycin, but Fosfomycin is more resistant to S. saprophyticus bacteria than levofloxaci.

Improving the Quality of Human Upper Urinary Tract Specimens by Cryobiopsy.

ObjectiveThe quality of histopathological specimens obtained from the upper urinary tract with conventional flexible ureterorenoscopic biopsy needs to be improved. We investigated the feasibility and biopsy quality of specimens obtained by cryobiopsy, compared with standard ureterorenoscopic biopsy techniques in a human ex vivo model.Materials and MethodsHuman ureters obtained from nephrectomy specimens (N=12) were dissected and canulated with an ureteral access sheath. Ureterorenoscopic biopsies were randomly obtained from different sites of the renal pelvic caliceal system using different types of instruments. The performance of two newly developed flexible cryoprobes with outer diameters of 1.1 mm (CB11) and 0.9 mm (CB09) was compared with that of the biopsy forceps(FB) and Bigopsy®(BiG) and two different Dormia baskets N‐Gage (NG) and Zero‐Tip (ZT). We assessed the feasibility of the various biopsy techniques based on the number of biopsy attempts needed to obtain macroscopically discernible biopsies. The specimens were examined histopathologically for size, biopsy quality, presence of various artifact types, and representativeness.ResultsBiopsies taken with the cryoprobes showed a higher biopsy quality than biopsies taken with the comparative instruments. The CB11 provided significantly larger biopsies than forceps biopsies and also than biopsies with ZT. The CB09 was able to collect larger samples when compared with the FB and BiG biopsy forceps. There were no significant differences in artifact area, except for the CB11 cryoprobe compared with the NG. To clarify the results a subdivision of larger or smaller than 20% artifact area was performed. A significant difference was found between CB11 and the forceps biopsies, as well as between CB11 and NG and ZT in favor of the cryoprobe. The representation of the histopathological sample was also determined. Biopsies taken with CB11 were more representative compared with forceps biopsies BiG and FB and basket biopsies NG and ZT.ConclusionsIn a standardized comparative ex vivo setting, larger biopsies were obtained by using the cryobiopsy technique with the CB11 probe. Qualitatively, cryobiopsy specimens were overlaid by fewer artifacts and a higher biopsy quality was achieved in histopathologic examination compared with standard instrumentation. Further stepwise development will transfer the promising cryobiopsy technique into the clinical setting.

Differential Afa/Dr Fimbriae Expression in the Multidrug-Resistant Escherichia coli ST131 Clone.

ABSTRACTMany antibiotic resistant uropathogenic Escherichia coli (UPEC) strains belong to clones defined by their multilocus sequence type (ST), with ST131 being the most dominant. Although we have a good understanding of resistance development to fluoroquinolones and third-generation cephalosporins by ST131, our understanding of the virulence repertoire that has contributed to its global dissemination is limited. Here we show that the genes encoding Afa/Dr fimbriae, a group of adhesins strongly associated with UPEC that cause gestational pyelonephritis and recurrent cystitis, are found in approximately one third of all ST131 strains. Sequence comparison of the AfaE adhesin protein revealed a unique allelic variant carried by 82.9% of afa-positive ST131 strains. We identify the afa regulatory region as a hotspot for the integration of insertion sequence (IS) elements, all but one of which alter afa transcription. Close investigation demonstrated that the integration of an IS1 element in the afa regulatory region leads to increased expression of Afa/Dr fimbriae, promoting enhanced adhesion to kidney epithelial cells and suggesting a mechanism for altered virulence. Finally, we provide evidence for a more widespread impact of IS1 on ST131 genome evolution, suggesting that IS dynamics contribute to strain level microevolution that impacts ST131 fitness.