Comparative study of virulence potential, phylogenetic origin, CRISPR-Cas regions and drug resistance of Escherichia coli isolates from urine and other clinical materials

IntroductionUrinary tract infections (UTI), among which the main etiological factor is uropathogenic Escherichia coli (UPEC, E. coli), remain an important issue for clinicians. The aim of the study was to demonstrate clear differences in the pathogenic properties of urine-derived E. coli compared to other extraintestinal E. coli clinical isolates (derived from: blood, lower respiratory tracts, sputum, reproductive tract, body fluids, perianal pus, other pus, wound, postoperative wound and other sources).MethodsThe collection of 784 E. coli isolates was collected from various materials of hospitalized patients. They were analyzed in terms of virulence-associated genes (papC, sfaD/sfaE, cnf1, usp., fimG/H, hlyA), belonging to phylogenetic groups and the presence of CRISPR-Cas regions using PCR. In addition, the epidemiological data and the antibiotic resistance profiles provided by the hospital’s microbiology department were included for statistical analyses.ResultsUrine-derived E. coli showed significantly greater virulence potential compared to other isolates, but they were generally unremarkable in terms of drug resistance. The isolates most often belonged to phylogenetic group B2. Drug resistance was negatively correlated with CRISPR 2 presence and high average virulence score, but positively correlated with CRISPR 4 presence. To the best of our knowledge, we are the first to report significant differences in sputum-derived isolates—they revealed the lowest virulence potential and, at the same time, the highest drug resistance.DiscussionIn conclusion, we demonstrated significant differences of urinary-derived E. coli compared to other clinical E. coli isolates. We would like to suggest excluding penicillins from use in E. coli infection at this time and monitoring strains with a high pathogenicity potential

Suppressor genes as molecular markers of colorectal cancer – a review of the latest reports

Suppressor gene research is one of the main current trends in modern cancer research. Oncogenesis, including colorectal cancer (CRC), is a process strictly dependent on the proper functioning of the suppressor genes and their proteins. The molecular genetic studies of hereditary cases and sporadic forms of cancer conducted for several years have revealed that a significant feature of the occurrence and progression of neoplastic changes is silencing of the expression of tissue-specific suppressor genes. Restoring the proper activity of the respective suppressor proteins plays a key role in anti-cancer prevention and gives hope for the development of effective personalised therapy. This review presents the latest reports on the molecular mechanisms regulating the expression, activity, and function of suppressor genes, which were silenced in tissues and cell lines of colorectal cancer, and restoration of their correct expression inhibited the proliferation and invasion of CRC cells

Iatrogenic Injury of Biliary Tree—Single-Centre Experience

Cholecystolithiasis is among the most prevalent gastrointestinal disorders requiring surgical intervention, and iatrogenic damage to the bile tree is a severe complication. We aimed to present the frequency of bile duct injuries and how our facility handles these complications. We retrospectively analyzed bile duct injuries in patients undergoing surgery. We concentrated on factors such as sex, age, indications for surgery, type of surgery, primary procedure, bile tree injury, repair, and timing as well as early and late complications. There were 22 cases of bile duct injury in the studied material, primarily affecting women—15 individuals (68.2%). Eleven cases (45.7%) of acute cholecystitis were the primary reason for surgery, and an injury to the common bile duct that extended up to 2 cm from the common hepatic duct was the most common complication (European Association for Endoscopic Surgery grade 2). Roux-en-Y hepaticojejunostomy was the most common repair procedure in 14 cases (63.6%). Eleven patients (50%) experienced early complications following reconstruction surgery, whereas five patients (22.7%) experienced late complications. An annual mortality rate of 22.7% (five patients) was observed. Iatrogenic bile duct injury is a severe complication of surgical treatment for cholecystolithiasis. Reconstruction procedures are characterized by high complication rates and high mortality

The Roles of TP53 and FGFR2 in Progress Made Treating Endometrial Cancer

The morbidity and mortality caused by endometrial cancer (EC) is still rising worldwide. In recent years, a new system of tumor stratification has been proposed based on POLE-mutational status, TP53, and microsatellite stability status. The aim of the study was to analyze a vast panel on the genes potentially involved in the genesis of endometrial cancer in the Polish population. One hundred and three white female patients with confirmed endometrial cancer were enrolled on the study. We performed sequencing using the Hot Spot Illumina panel and microsatellite stability with immunohistochemistry. We confirmed a key role of the TP53 mutation in progress to high-grade EC and parallelly some role of FGFR2 mutation. Moreover, our data present a vast landscape of mutations in EC and their polymorphism. We reported the meaning of FGFR2 mutation and TP53 (high copy number) in high-grade ECs. Our observation in MSI contribution is comparable with other studies. Finally, we see a strong need for the implementation of the TCGA classification

Endometrial Cancer in Aspect of Forkhead Box Protein Contribution

(1) Background: The present study aimed to investigate the influence of forkhead box (FOX) on endometrial cancer (EC) progression. For a better understanding, the driving mechanisms are vital to identifying correlations between genes and their regulators. (2) Methods: The study enrolled one hundred and three white female patients with confirmed EC. For the analysis, we used next-generation sequencing with the Hot Spot Cancer Panel provided by Illumina Inc., San Diego, CA, USA, and an immunohistochemical analysis of FOXA1, FOXP1, and estrogen receptors. (3) Results: FOXA1 silencing led to a worse outcome based on the correlation with FOXA1 (test log-rank p = 0.04220 and HR 2.66, p = 0.033). Moreover, FOX proteins were closely correlated with TP53 and KRAS mutation. (4) Conclusions: Our study confirmed previous reports about FOX box protein in the regulation of tumor growth. A remarkable observation about the unclear crosstalk with crucial genes, as TP53 and KRAS need deeper investigation

FGFR-2 and Epithelial–Mesenchymal Transition in Endometrial Cancer

Background. At present, EC staging is based on the WHO conservative criteria, which only consider the percentage of gland formation. The molecular subgrouping of EC recently proposed by the Cancer Genome Atlas (TCGA) represents a milestone in precise molecular-based patient triage. The present study aimed to investigate the influence of FGFR-2 on the epithelial–mesenchymal transition (EMT) and whether it can lead to endometrial cancer dedifferentiation. Methods. One hundred and three White female patients with confirmed EC were enrolled in our research. For the analysis, we performed next-generation sequencing and immunohistochemical analyses of E-cadherin, β-catenin, and vimentin. Results. Tumor grade progression was closely correlated with LVI (p = 0.0338), expression of vimentin (p = 0.000), tumor budding (p = 0.000), and lack of E-cadherin (p = 0.0028). Similar observations were noted with regard to TNM/FIGO stage progression. In terms of FGFR-2 mutation, we found the following correlation p-values: LVI (p = 0.069), expression of vimentin (p = 0.000), tumor budding (p = 0.000), and lack of E-cadherin (p = 0.000), RFS (p = 0.032), ECSS (p = 0.047). Conclusions. FGFR-2 is the important factor influencing on EMT

Ciprofloxacin, amoxicillin, and aminoglycosides stimulate genetic and phenotypic changes in uropathogenic Escherichia coli strains

Antibiotic therapy and its consequences in bacterial and human aspects are widely investigated. Despite this, the emergence of new multidrug resistant bacteria is still a current problem. The scope of our work included the observation of changes among uropathogenic Escherichia coli strains after the treatment with a subinhibitory concentration of different antibiotics. The sensitive strains with or without virulence factors were incubated with amoxicillin, ciprofloxacin, gentamycin, or tobramycin. After each passage, the E. coli derivatives were compared to their wild types based on their susceptibility profiles, virulence genes, biofilm formations and the fingerprint profiles of PCR products amplified with using the (N)(6)(CGG)(4) primer. It turned out that antibiotics caused significant changes in the repertoire of bacterial virulence and biofilm formation, corresponding to acquired cross-resistance. The genomic changes among the studied bacteria were reflected in the changed profiles of the CGG-PCR products. In conclusion, the inappropriate application of antibiotics may cause a rapid rise of Multidrug Resistant (MDR) strains and give bacteria a chance to modulate their own pathogenicity. This phenomenon has been easily observed among uropathogenic E. coli strains and it is one of the main reasons for recurrent infections of the urinary tract

Glutathione S-Transferase P1 Genetic Variant’s Influence on the HbA1c Level in Type Two Diabetic Patients

GST (glutathione S-transferases) are capable of influencing glucose homeostasis, probably through regulation of the response to oxidant stress. The aim of our study was to investigate the relationship between GSTP1 gene polymorphism and glycated hemoglobin (HbA1c) levels in type two diabetic (T2D) patients. A total of 307 T2D patients were included. Analysis of the GSTP1 gene polymorphism (rs1695) was conducted using the TaqMan qPCR method endpoint genotyping. HbA1c was determined using a COBAS 6000 autoanalyzer. A univariable linear regression and multivariable linear regression model were used to investigate the association between mean HbA1c level and GSTP1 gene polymorphism, age at T2D diagnosis, T2D duration, therapy with insulin, gender, BMI, smoking status. GSTP1 Val/Val genotype, age at T2D diagnosis, T2D duration and therapy with insulin were statistically significant contributors to HbA1c levels (p p = 0.024). The results suggest that GSTP polymorphism may be one of the risk factors for higher HbA1c in T2D patients. Our study is limited by the relatively small sample size, cross-sectional design, and lack of inclusion of other oxidative stress-related genetic variants

NOS2 Polymorphism in Aspect of Left and Right-Sided Colorectal Cancer

Background: The NOS2 gene polymorphism rs2297518 is associated with an increased level of NO, which could contribute to colorectal cancer (CRC) development. We hypothesized that the potential influence of the NOS2 gene polymorphism on cancer development may vary between right-sided and left-sided colon cancers, and rectal cancers. The aim of this study was to determine the rs2297518 polymorphism influence on colorectal cancer development with regard to tumor localization. Methods: This case–control study included 199 patients with CRC and 120 controls. The qPCR endpoint genotyping was conducted using the TaqMan® genotyping assay. Results: This study revealed significant differences in tumor characteristic and in the minor alelle A frequency in the NOS2 genotype between colorectal cancers with different localizations. The mucinous adenocarcinoma was diagnosed significantly more often in right-sided cancers than in left-sided (30.6% vs. 10.9%, p = 0.009) and rectal cancers (30.6% vs. 7.1%, p = 0.0003). The minor allele A of the NOS2 genotype was observed more frequently in right-sided cancers than in left-sided cancers (44.9% vs. 23.1%, p = 0.0137) and more frequently in rectal cancers than in left-sided cancers (40.0% vs. 23.1%, p = 0.0285). Conclusions: In conclusion, the results support the hypothesis that the SNP rs2297518 of the NOS2 gene influences colorectal cancer development with regard to tumor localization