Search Results (11)

Urinary tract infections (UTIs) are one of the most frequent bacterial infections in the world, both in the hospital and community settings. Uropathogenic Escherichia coli (UPEC) are the predominant etiological agents causing UTIs. Extended-spectrum beta-lactamase (ESBL) production is a prominent mechanism of resistance that hinders the antimicrobial treatment of UTIs caused by UPEC and poses a substantial danger to the arsenal of antibiotics now in use. As bacteria have several methods to counteract the effects of antibiotics, identifying new potential drug targets may help in the design of new antimicrobial agents, and in the control of the rising trend of antimicrobial resistance (AMR). The public availability of the entire genome sequences of humans and many disease-causing organisms has accelerated the hunt for viable therapeutic targets. Using a unique, hierarchical, in silico technique using computational tools, we discovered and described potential therapeutic drug targets against the ESBL-producing UPEC strain NA114. Three different sets of proteins (chokepoint, virulence, and resistance genes) were explored in phase 1. In phase 2, proteins shortlisted from phase 1 were analyzed for their essentiality, non-homology to the human genome, and gut flora. In phase 3, the further shortlisted putative drug targets were qualitatively characterized, including their subcellular location, broad-spectrum potential, and druggability evaluations. We found seven distinct targets for the pathogen that showed no similarity to the human proteome. Thus, possibilities for cross-reactivity between a target-specific antibacterial and human proteins were minimized. The subcellular locations of two targets, ECNA114_0085 and ECNA114_1060, were predicted as cytoplasmic and periplasmic, respectively. These proteins play an important role in bacterial peptidoglycan biosynthesis and inositol phosphate metabolism, and can be used in the design of drugs against these bacteria. Inhibition of these proteins will be helpful to combat infections caused by MDR UPEC. Full article

(1) Background: Pathogenic Escherichia coli are divided into two groups: diarrheagenic (DEC) and extraintestinal pathogenic (ExPEC) E. coli. ExPEC causing urinary tract infections (UTIs) are termed uropathogenic E. coli (UPEC) and are the most common cause of UTIs worldwide. (2) Methods: Here, we characterized 112 UPEC in terms of phylogroup, serotype, the presence of virulence factor-encoding genes, and antimicrobial resistance. (3) Results: The majority of the isolates were assigned into the phylogroup B2 (41.07%), and the serogroups O6 (12.5%) and O25 (8.9%) were the most frequent. Five hybrid UPEC (4.5%), with markers from two DEC pathotypes, i.e., atypical enteropathogenic (aEPEC) and enteroaggregative (EAEC) E. coli, were identified, and designated UPEC/aEPEC (one isolate) and UPEC/EAEC (four isolates), respectively. Three UPEC/EAEC harbored genes from the pap operon, and the UPEC/aEPEC carried ibeA. The highest resistance rates were observed for ampicillin (46.4%) and trimethoprim/sulfamethoxazole (34.8%), while 99.1% of the isolates were susceptible to nitrofurantoin and/or fosfomycin. Moreover, 9.8% of the isolates were identified as Extended Spectrum β-Lactamase producers, including one hybrid UPEC/EAEC. (4) Conclusion: Our data reinforce that hybrid UPEC/DEC are circulating in the city of Botucatu, Brazil, as uropathogens. However, how and whether these combinations of genes influence their pathogenicity is a question that remains to be elucidated. Full article

The role of uropathogenic Escherichia coli (UPEC) in colonization and infection of female patients with anatomical and functional abnormalities of the urinary system is elusive. In this study, the phenotype, genotype and the phylogeny of UPEC strains isolated from the urine of pediatric female patients with cystitis of normal and abnormal urinary tract were determined. Multiplex PCR results demonstrated that 86% of the strains isolated from female patients with normal urinary tract (NUT), belonged to the phylo-groups B2 and D. Their prevalence decreased to 23% in strains isolated from patients with abnormal urinary tract (AUT). More of the isolates from AUT patients produced a biofilm on polystyrene and polyvinyl chloride (PVC), adhered to epithelial cells, and encoded pap and sfa genes than strains isolated from female patients with NUT. In contrast, a higher number of hemolysin-producing strains with serogroups associated with UPEC were isolated from patients with NUT. In summary, the results suggest that cystitis in female patients with NUT is associated with ExPEC, whereas cystitis in female patients with AUT is associated with pathogenic intestinal E. coli strains that have acquired the ability to colonize the bladder. Full article

Antimicrobial bacteria resistance is an important problem in children with recurrent urinary tract infections (rUTI), thus it is crucial to search for alternative therapies. Autologous bacterial lysates (ABL) may be a potential treatment for rUTI. Twenty-seven children with rUTI were evaluated for one year, urine and stool cultures were performed, 10 colonies of each culture were selected and those identified as Escherichia coli were characterized by serology. For patients who presented ≥10⁵ UFC/mL, an ABL was manufactured and administered orally (1 mL/day) for a month. Twelve children were monitored for ≥1-year, 218 urine and 11 stool samples were analyzed. E. coli (80.5%) was the main bacteria isolated from urine and feces (72%). E. coli of classical urinary serotypes (UPEC), O25:H4, O75:HNM, and O9:HNM were identified in patients with persistent urinary infection (pUTI). In 54% of patients treated with ABL, the absence of bacteria was observed in urine samples after 3 months of treatment, 42% of these remained without UTI between 10–12 months. It was observed that the use of ABL controlled the infection for almost 1 year in more than 60% of the children. We consider it necessary to develop a polyvalent immunogen for the treatment and control of rUTI. Full article

(1) Background: Hybrid uropathogenic Escherichia coli (UPEC) strains carry virulence markers of the diarrheagenic E. coli (DEC) pathotypes, which may increase their virulence potential. This study analyzed the frequency and virulence potential of hybrid strains among 452 UPEC strains. (2) Methods: Strains were tested for the DEC virulence diagnostic genes’ presence by polymerase chain reaction (PCR). Those carrying at least one gene were classified as hybrid and further tested for 10 UPEC and extraintestinal pathogenic E. coli (ExPEC) virulence genes and phylogenetic classification. Also, their ability to produce hemolysis, adhere to HeLa and renal HEK 293T cells, form a biofilm, and antimicrobial susceptibility were evaluated. (3) Results: Nine (2%) hybrid strains were detected; seven of them carried aggR and two, eae, and were classified as UPEC/EAEC (enteroaggregative E. coli) and UPEC/aEPEC (atypical enteropathogenic E. coli), respectively. They belonged to phylogroups A (five strains), B1 (three), and D (one), and adhered to both cell lineages tested. Only the UPEC/EAEC strains were hemolytic (five strains) and produced biofilm. One UPEC/aEPEC strain was resistant to third-generation cephalosporins and carried bla_CTX-M-15. (4) Conclusions: Our findings contribute to understanding the occurrence and pathogenicity of hybrid UPEC strains, which may cause more severe infections. Full article

The great plasticity and diversity of the Escherichia coli genome, together with the ubiquitous occurrence, make E. coli a bacterium of world-wide concern. Of particular interest are pathogenic strains and strains harboring antimicrobial resistance genes. Overlapping virulence-associated traits between avian-source E. coli and human extraintestinal pathogenic E. coli (ExPEC) suggest zoonotic potential and safety threat of poultry food products. We analyzed whole-genome sequencing (WGS) data of 46 mcr-1-positive E. coli strains isolated from retail raw meat purchased in the Czech Republic. The investigated strains were characterized by their phylogroup—B1 (43%), A (30%), D (11%), E (7%), F (4%), B2 (2%), C (2%), MLST type, and serotype. A total of 30 multilocus sequence types (STs), of which ST744 was the most common (11%), were identified, with O8 and O89 as the most prevalent serogroups. Using the VirulenceFinder tool, 3 to 26 virulence genes were detected in the examined strains and a total of 7 (15%) strains met the pathogenic criteria for ExPEC. Four strains were defined as UPEC (9%) and 18 (39%) E. coli strains could be classified as APEC. The WGS methods and available on-line tools for their evaluation enable a comprehensive approach to the diagnosis of virulent properties of E. coli strains and represent a suitable and comfortable platform for their detection. Our results show that poultry meat may serve as an important reservoir of strains carrying both virulence and antibiotic resistance genes for animal and human populations. Full article

Under a one health perspective and the worldwide antimicrobial resistance concern, we investigated extraintestinal pathogenic Escherichia coli (ExPEC), uropathogenic E. coli (UPEC), and multidrug resistant (MDR) E. coli from 197 isolates recovered from healthy dogs in Spain between 2013 and 2017. A total of 91 (46.2%) isolates were molecularly classified as ExPEC and/or UPEC, including 50 clones, among which (i) four clones were dominant (B2-CH14-180-ST127, B2-CH52-14-ST141, B2-CH103-9-ST372 and F-CH4-58-ST648) and (ii) 15 had been identified among isolates causing extraintestinal infections in Spanish and French humans in 2015 and 2016. A total of 28 (14.2%) isolates were classified as MDR, associated with B1, D, and E phylogroups, and included 24 clones, of which eight had also been identified among the human clinical isolates. We selected 23 ST372 strains, 21 from healthy dogs, and two from human clinical isolates for whole genome sequencing and built an SNP-tree with these 23 genomes and 174 genomes (128 from canine strains and 46 from human strains) obtained from public databases. These 197 genomes were segregated into six clusters. Cluster 1 comprised 74.6% of the strain genomes, mostly composed of canine strain genomes (p < 0.00001). Clusters 4 and 6 also included canine strain genomes, while clusters 2, 3, and 5 were significantly associated with human strain genomes. Finding several common clones and clone-related serotypes in dogs and humans suggests a potentially bidirectional clone transfer that argues for the one health perspective. Full article

The aim of the present study was to characterize Enterobacterales resistant to 3rd and 4th generation cephalosporins, carbapenems and/or fluoroquinolones, isolated from dogs and cats with urogenital infections. In total, 36 strains (Escherichia coli (n = 28), Klebsiella pneumoniae (n = 3), Serratia marcescens, Raoultella ornithinolytica, Proteus mirabilis, Citrobacter portucalensis and Enterobacter cloacae (each n = 1)) were included in the present study, 28 from Austria and 8 from Serbia. Isolates were characterized by a polyphasic approach including susceptibility pheno- and genotyping and microarray-based assays. Escherichia (E.) coli isolates were additionally characterized by two-locus (fumC and fimH) sequence phylotyping and multi-locus sequence typing (MLST) of selected isolates. MLST of carbapenem-resistant Enterobacter cloacae isolates was also performed. Among E. coli, the most dominant phylogenetic group was B1 (27.8%), followed by C, (16.6%), A and Clade II (5.5% each), B2 and F (2.77% each). The most predominant β-lactam resistance genes were bla_TEM (70%) and bla_CTX-M (38.8%), bla_CMY (25%). bla_NDM was detected in one carbapenem-resistant Enterobacter cloacae ST114. The most common ST among selected E. coli was 744 (10.7% isolates). The pandemic clones ST131 and ST648 carrying CTX-M-15 were also detected. Remaining STs belonged to 469, 1287, 1463 and 1642. E. coli clonotyping revealed 20 CH types. Based on the presence of certain virulence genes, three isolates were categorized as ExPEC/UPEC. The most prevalent virulence factors were fimH detected in 61%, iucD and iss both in 55%, iroN in 27.8%, papC in 13.8% and sat in 8.3% isolates. Full article

The Guangdong–Hong Kong–Macau Greater Bay Area (GBA) of China is one of the major bay areas in the world. However, the spatiotemporal characteristics and rationalities of urban expansions within this region over a relatively long period of time are not well-understood. This study explored the spatiotemporal evolution of 11 cities within the GBA in 1987–2017 by integrating remote sensing, landscape analysis, and geographic information system (GIS) techniques, and further evaluated the rationalities of their expansion using the urban area population elastic coefficient (UPEC) and the urban area gross domestic product (GDP) elastic coefficient (UGEC). The results showed the following: (1) Guangzhou, Shenzhen, Foshan, Dongguan, Zhongshan, and Zhuhai experienced unprecedented urbanization compared with the other cities, and from 1987 to 2017, their urban areas expanded by 10.12, 11.48, 14.21, 24.90, 37.07, and 30.15 times, respectively; (2) several expansion patterns were observed in the 11 cities, including a mononuclear polygon radiation pattern (Guangzhou and Foshan), a double-nucleated polygon pattern (Macau and Zhongshan), and a multi-nuclear urbanization pattern (Shenzhen, Hong Kong, Dongguan, Jiangmen, Huizhou, Zhaoqing, and Zhuhai); (3) with regard to the proportion of area, the edge-expansion and outlying growth types were the predominant types for all 11 cities, and the infilling growth type was the one of the important types during 2007–2017 for Shenzhen, Hong Kong, Dongguan, Zhongshan, and Foshan; (4) the expansion of most cities took on an urban-to-rural landscape gradient, especially for Guangzhou, Shenzhen, Foshan, Zhongshan, Dongguan, and Zhuhai; and (5) the rationalities of expansion in several time periods were rational for Guangzhou (1997–2007), Hong Kong (2007–2017), Foshan (1987–2007), Huizhou (1987–1997), and Dongguan (1997–2007), and the rationalities of expansion in the other cities and time periods were found to be irrational. These findings may help policy- and decision-makers to maintain the sustainable development of the Guangdong–Hong Kong–Macau Greater Bay Area. Full article

Urinary tract infections (UTI) are the most common hospital-acquired infections in humans and are caused primarily by uropathogenic Escherichia coli (UPEC). Indwelling urinary catheters become encrusted with UPEC biofilms that are resistant to common antibiotics, resulting in chronic infections. Therefore, it is important to control UPEC biofilms on catheters to reduce the risk for UTIs. This study investigated the efficacy of selenium for inhibiting and inactivating UPEC biofilms on urinary catheters. Urinary catheters were inoculated with UPEC and treated with 0 and 35 mM selenium at 37 °C for 5 days for the biofilm inhibition assay. In addition, catheters with preformed UPEC biofilms were treated with 0, 45, 60, and 85 mM selenium and incubated at 37 °C. Biofilm-associated UPEC counts on catheters were enumerated on days 0, 1, 3, and 5 of incubation. Additionally, the effect of selenium on exopolysacchride (EPS) production and expression of UPEC biofilm-associated genes was evaluated. Selenium at 35 mM concentration was effective in preventing UPEC biofilm formation on catheters compared to controls (p < 0.05). Further, this inhibitory effect was associated with a reduction in EPS production and UPEC gene expression. Moreover, at higher concentrations, selenium was effective in inactivating preformed UPEC biofilms on catheters as early as day 3 of incubation. Results suggest that selenium could be potentially used in the control of UPEC biofilms on urinary catheters. Full article

Urinary tract infections (UTIs) are one of the most important causes of morbidity and health care spending affecting persons of all ages. Bacterial biofilms play an important role in UTIs, responsible for persistent infections leading to recurrences and relapses. UTIs associated with microbial biofilms developed on catheters account for a high percentage of all nosocomial infections and are the most common source of Gram-negative bacteremia in hospitalized patients. The purpose of this mini-review is to present the role of microbial biofilms in the etiology of female UTI and different male prostatitis syndromes, their consequences, as well as the challenges for therapy Full article