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Urinary tract infections (UTIs) belong to the most common community-acquired and nosocomial infections. A main etiological factor of UTIs is uropathogenic (UPEC). This review describes the current state of knowledge on the resistance of UPEC to antibiotics recommended for the treatment of UTIs based on the available literature data. Nitrofurantoin and fosfomycin are recommended as first-line therapy in the treatment of uncomplicated cystitis, and the resistance to these antimicrobial agents remains low between UPEC. Recently, in many countries, the increasing resistance is observed to trimethoprim-sulfamethoxazole, which is widely used as the first-line antimicrobial in the treatment of uncomplicated UTIs. In European countries, the resistance of UPEC to this antimicrobial agent ranges from 14.6% to 60%. The widespread use of fluoroquinolones (FQs), especially ciprofloxacin, in the outpatients is the cause of a continuous increase in resistance to these drugs. The resistance of UPEC to FQs is significantly higher in developing countries (55.5–85.5%) than in developed countries (5.1–32.0%). Amoxicillin-clavulanic acid is recommended as first line-therapy for pyelonephritis or complicated UTI. Resistance rates of UPEC to amoxicillin-clavulanic acid are regionally variable. In European countries the level of resistance to this antimicrobial ranges from 5.3% (Germany) to 37.6% (France). Increasing rates of UPEC resistance to antimicrobials indicate that careful monitoring of their use for UTI treatment is necessary.

Background Urinary Tract Infection (UTI) is one of the most common bacterial infectious diseases which causes considerable morbidity and costly health problems. Uropathogenic Escherichia coli (UPEC), the most common pathogen causing UTI, is a highly heterogeneous group of extraintestinal pathogenic E. coli (ExPEC) which may carry a variety of virulence factors and belonging to different phylogenetic backgrounds. The current study aimed to investigate the frequency and association between various virulence factors (VFs) and phylogenetic groups of UPEC and commensal isolates. Methods UPEC and commensal E. coli strains isolated from UTI and feces of healthy humans were compared for the presence of VFs and phylogenetic groups. Association between virulence genes was investigated and cluster analysis was employed. Results According to the results, among a 30 virulence markers tested, the pathogenicity-associated island (PAI) , pap AH, papEF , fimH, fyuA , and traT genes prevalence were statistically significant in UPEC isolates. A strong association was found between the B2 and D phylogenetic groups and clinical isolates of UPEC; while, commensal isolates were mostly associated with phylogenetic group A. The aggregated VFs scores were more than twice higher in the UPEC isolates in comparison with the commensal isolates. Interestingly, the B2 group in both UPEC and commensal isolates had the highest VF scores. A strong positive association was found between several virulence genes. The clustering results demonstrated that UPEC or commensal E. coli isolates were highly heterogeneous due to different composition of their virulence gene pool and pathogenicity islands. Conclusion Genetic structure and VFs of UPEC strains vary from region to region; therefore, to control the UTI, the epidemiological aspects and characterization of the UPEC isolates need to be investigated in different regions. Since UPEC isolates are generally originate from the commensal strains, it may be feasible to reduce the UTI burden by interfering the intestinal colonization, particularly in the highly pathogenic clonal lineages such as B2.

Both F17-like and type 1 pili promote intestinal colonization in mouse colonic crypts, and the high-affinity mannoside M4284 reduces intestinal colonization of uropathogenic Escherichia coli while simultaneously treating urinary tract infections without disrupting the composition of the gut microbiota. UTI reduction by mannoside Uropathogenic E. coli (UPEC) are responsible for 80% of community-acquired and 65% of nosocomial urinary tract infections (UTI), which together affect 150 million people annually. UPEC establishes reservoirs in the gut, but the factors involved in this process have remained unknown. Here, Scott Hultgren and colleagues show that both F17-like and type 1 pili promote intestinal colonization and bind to distinct glycans on epithelial cells distributed along colonic crypts. Using the high-affinity mannose analogue, mannoside M4284, which inhibits the adhesive function of type 1 pili, the authors demonstrate that it effectively reduces intestinal colonization of UPEC, while simultaneously treating UTI without significantly disrupting the composition of the gut microbiota. The authors suggest that this selective depletion of intestinal UPEC by mannosides could be used to reduce the occurrence of UTIs. Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) affect 150 million people annually 1 , 2 . Despite effective antibiotic therapy, 30–50% of patients experience recurrent UTIs 1 . In addition, the growing prevalence of UPEC that are resistant to last-line antibiotic treatments, and more recently to carbapenems and colistin, make UTI a prime example of the antibiotic-resistance crisis and emphasize the need for new approaches to treat and prevent bacterial infections 3 , 4 , 5 . UPEC strains establish reservoirs in the gut from which they are shed in the faeces, and can colonize the periurethral area or vagina and subsequently ascend through the urethra to the urinary tract, where they cause UTIs 6 . UPEC isolates encode up to 16 distinct chaperone-usher pathway pili, and each pilus type may enable colonization of a habitat in the host or environment 7 . For example, the type 1 pilus adhesin FimH binds mannose on the bladder surface, and mediates colonization of the bladder. However, little is known about the mechanisms underlying UPEC persistence in the gut 5 . Here, using a mouse model, we show that F17-like and type 1 pili promote intestinal colonization and show distinct binding to epithelial cells distributed along colonic crypts. Phylogenomic and structural analyses reveal that F17-like pili are closely related to pilus types carried by intestinal pathogens, but are restricted to extra-intestinal pathogenic E. coli . Moreover, we show that targeting FimH with M4284, a high-affinity inhibitory mannoside, reduces intestinal colonization of genetically diverse UPEC isolates, while simultaneously treating UTI, without notably disrupting the structural configuration of the gut microbiota. By selectively depleting intestinal UPEC reservoirs, mannosides could markedly reduce the rate of UTIs and recurrent UTIs.

The emergence and spread of antibiotic-resistant bacteria are aggravated by incorrect prescription and use of antibiotics. A core problem is that there is no sufficiently fast diagnostic test to guide correct antibiotic prescription at the point of care. Here, we investigate if it is possible to develop a point-of-care susceptibility test for urinary tract infection, a disease that 100 million women suffer from annually and that exhibits widespread antibiotic resistance. We capture bacterial cells directly from samples with low bacterial counts (10⁴ cfu/mL) using a custom-designed microfluidic chip and monitor their individual growth rates using microscopy. By averaging the growth rate response to an antibiotic over many individual cells, we can push the detection time to the biological response time of the bacteria. We find that it is possible to detect changes in growth rate in response to each of nine antibiotics that are used to treat urinary tract infections in minutes. In a test of 49 clinical uropathogenic Escherichia coli (UPEC) isolates, all were correctly classified as susceptible or resistant to ciprofloxacin in less than 10 min. The total time for antibiotic susceptibility testing, from loading of sample to diagnostic readout, is less than 30 min, which allows the development of a point-of-care test that can guide correct treatment of urinary tract infection.

Background Uropathogenic Escherichia coli (UPEC) is the predominant cause of urinary tract infections (UTIs), and the recurrence of these infections poses significant treatment challenges. Objective This study aimed to compare the phylogroups, biofilm formation, virulence factors, and antibiotic resistance of UPEC strains in patients with recurrent versus non-recurrent UTIs in Hamadan City, Western Iran. Materials and methods A total of 110 E. coli isolates were collected from urine cultures across three major hospitals and laboratories. The isolates were confirmed through biochemical tests, and their antibiotic resistance profiles were evaluated using the disk diffusion method. Biofilm production was assessed using the microtiter plate method, while virulence genes and phylogroup determination were analyzed via PCR. Real-time PCR was employed to compare the expression levels of the pap and fim H virulence genes. Results The results indicated that 73% of isolates were from non-recurrent UTI patients, with a higher incidence in females and children under 10 years. A significant difference was detected in the underlying diseases and the expression of the pap between the recurrent and non-recurrent groups. Antibiotic resistance was notably significant, particularly against Ampicillin-sulbactam, Trimethoprim-Sulfamethoxazole, Nalidixic acid, and Ciprofloxacin, with 77% of strains classified as multi-drug resistant (MDR). Despite differences in the rates of ESBL production between recurrent (53%) and non-recurrent (42.5%) strains, no significant differences were observed in antibiotic resistance, biofilm formation, virulence factors, or phylogroups between the two groups. Phylogenetic analysis revealed a predominance of phylogroups B2 and D, with high genetic diversity among the isolates. Conclusion The study highlights the traits of UPEC strains in recurrent and non-recurrent UTIs, showing high antibiotic resistance and genetic diversity among isolates. The study found notable differences in underlying diseases and the expression of the pap gene between recurrent and non-recurrent groups, suggesting that these factors may play a crucial role in the recurrence of infections. Further investigation into these differences could enhance our understanding and management of recurrent UTIs.

Carbapenem-resistant Enterobacterales pose a critical global health threat, exemplified by increasing resistance of uropathogenic E. coli (UPEC) that cause urinary tract infections (UTIs). Here, we investigate the publicly available EnteroBase dataset and identify a signal of increasing UTI caused by phylogroup A E. coli sequence type 167 (ST167). Phylogenetic analysis of ST167 based on whole genome sequence data reveal three major clades (A, B, C), with clade C further resolving into several subclades, notably subclade C2 that possessed high carriage rates of carbapenem and cephalosporin resistance genes. Hierarchical clustering of core genome multi-locus sequence typing reveals ~77% of subclade C2 strains contain <20 allelic differences in 2,513 core genes and harbour two distinct group 1 capsule types, KL124 and KL30, likely originating from Klebsiella . Subclade C2 was predominantly sequenced in North America, and we provide evidence for clonal expansion since 2016. Analysis of UPEC virulence factors reveals complete loss of the type 1 fimbriae genes in strains from clades B and C. Two subclade C2 isolates exhibit significantly reduced capacity to colonise the bladder compared to the reference UPEC strain CFT073 in a murine UTI model. Collectively, our data identifies ST167 as an atypical UPEC clone associated with UTI. Antibiotic resistance poses a critical global health threat. Here, the authors identify a carbapenem resistant clone of uropathogenic Escherichia coli with atypical virulence features as an increasing cause of urinary tract infection

Urinary tract infections (UTIs) are among the most common bacterial infections, causing considerable morbidity in females. Infection is highly recurrent despite appropriate antibiotic treatment. Uropathogenic Escherichia coli (UPEC), the most common causative agent of UTIs, invades bladder epithelial cells (BECs) and develops into clonal intracellular bacterial communities (IBCs). Upon maturation, IBCs disperse, with bacteria spreading to neighboring BECs to repeat this cycle. This process allows UPEC to gain a foothold in the face of innate defense mechanisms, including micturition, epithelial exfoliation, and the influx of polymorphonuclear leukocytes. Here, we investigated the mechanism and dynamics of urothelial exfoliation in the early acute stages of infection. We show that UPEC α-hemolysin (HlyA) induces Caspase-1/Caspase-4–dependent inflammatory cell death in human urothelial cells, and we demonstrate that the response regulator (CpxR)-sensor kinase (CpxA) two-component system (CpxRA), which regulates virulence gene expression in response to environmental signals, is critical for fine-tuning HlyA cytotoxicity. Deletion of the cpxR transcriptional response regulator derepresses hlyA expression, leading to enhanced Caspase-1/Caspase-4– and NOD-like receptor family, pyrin domain containing 3-dependent inflammatory cell death in human urothelial cells. In vivo, overexpression of HlyA during acute bladder infection induces more rapid and extensive exfoliation and reduced bladder bacterial burdens. Bladder fitness is restored fully by inhibition of Caspase-1 and Caspase-11, the murine homolog of Caspase-4. Thus, we have discovered that fine-tuning of HlyA expression by the CpxRA system is critical for enhancing UPEC fitness in the urinary bladder. These results have significant implications for our understanding of how UPEC establishes persistent colonization. Significance The majority of urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC). Upon UPEC infection, exfoliation of host bladder epithelial (urothelial) cells leads to sloughing of bacteria-laden cells into the urine for expulsion. However, it can also facilitate bacterial dissemination into deeper tissues. Thus, the balance and timing of exfoliation are important in determining disease outcomes. Here, we investigate host–pathogen dynamics in human urothelial cells in vitro and in murine model of acute cystitis. We discovered that the CpxR response regulator-CpxA sensor kinase two-component system regulates the expression of the pore-forming toxin α-hemolysin (HlyA) in response to environmental conditions. HlyA, in turn, is critical for fine-tuning the dynamics of host cell exfoliation and enhancing UPEC fitness during acute UTI.

Introduction Uropathogenic E. coli is the leading cause of Urinary tract infections (UTIs), contributing to 80–90% of all community-acquired and 30–50% of all hospital-acquired UTIs. Biofilm forming Uropathogenic E. coli are associated with persistent and chronic inflammation leading to complicated and or recurrent UTIs. Biofilms provide an environment for poor antibiotic penetration and horizontal transfer of virulence genes which favors the development of Multidrug-resistant organisms (MDRO). Understanding biofilm formation and antimicrobial resistance determinants of Uropathogenic E. coli strains will provide insight into the development of treatment options for biofilm-associated UTIs. The aim of this study was to determine the biofilm forming capability, presence of virulence genes and antimicrobial susceptibility pattern of Uropathogenic E. coli isolates in Uganda. Methods This was a cross-sectional study carried in the Clinical Microbiology and Molecular biology laboratories at the Department of Medical Microbiology, Makerere University College of Health Sciences. We randomly selected 200 Uropathogenic E. coli clinical isolates among the stored isolates collected between January 2018 and December 2018 that had significant bacteriuria (> 10 5  CFU). All isolates were subjected to biofilm detection using the Congo Red Agar method and Antimicrobial susceptibility testing was performed using the Kirby disk diffusion method. The isolates were later subjected PCR for the detection of Urovirulence genes namely; Pap, Fim, Sfa, Afa, Hly and Cnf, using commercially designed primers. Results In this study, 62.5% (125/200) were positive biofilm formers and 78% (156/200) of these were multi-drug resistant (MDR). The isolates were most resistant to Trimethoprim sulphamethoxazole and Amoxicillin (93%) followed by gentamycin (87%) and the least was imipenem (0.5%). Fim was the most prevalent Urovirulence gene (53.5%) followed by Pap (21%), Sfa (13%), Afa (8%), Cnf (5.5%) and Hyl (0%). Conclusions We demonstrate a high prevalence of biofilm-forming Uropathogenic E. coli strains that are highly associated with the MDR phenotype. We recommend routine surveillance of antimicrobial resistance and biofilm formation to understand the antibiotics suitable in the management of biofilm-associated UTIs.

Escherichia coli is arguably one of the most studied bacterial model systems in modern biology. While E. coli are normally rod-shaped gram-negative bacteria, they are known to undergo conditional morphology changes under environmental and nutrient stress. In this study, using an infection-based in-vitro infection model system combined with advanced dynamical imaging, we present the first molecular details of uropathogenic E. coli (UPEC) dividing to form and proliferate as coccoid-shaped cells inside human host cells. For these intracellular UPEC cells, the frequency of cell division outpaced the rate of cell growth, resulting in a morphological transition from traditional rod-shape to coccobacilli. We also visualized the subcellular protein dynamics in these cells and noted that the division proteins follow the similar localization and constriction patterns that have been demonstrated for vegetative growth. However, unlike for fast-growing rod-shaped cells, FtsZ constriction in intracellular UPEC occurs prior to visual nucleoid segregation. Our results suggest that the modulation of division rate contributes to morphological adaptability of intracellular UPEC at the single-cell level.

Background Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC) belonging to global strains such as ST-131 pose a significant health challenge. To understand the evolutionary landscape and molecular mechanisms defining ST-131 UPEC, the complete genome of E. coli NS30 was generated and analyzed. Results The complete genome assembly of E. coli NS30, belonging to high-risk ST-131, C2 subclade, revealed a chromosome and two plasmids. A large conjugative plasmid, pNS30-1, harboured a multi-drug resistance (MDR) cassette within a Tn402-like class 1 integron, which was functionally demonstrated to be transferable. Comparative genomic analysis identified four distinct genomic islands (GIs) that are absent in its closest ST-131 neighbour. Two of these, including a novel pathogenicity island (PAI), were acquired from other E. coli lineages, harbouring Virulence factors (VFs) and efflux pump genes. The remaining two GIs are phage-like elements contributing to genome plasticity. Conclusions E. coli NS30 is distinct from the other ST-131 UPEC genomes by the acquisition of novel GIs. The presence of GIs, virulence factors and AMR genes in a conjugative MDR plasmid has driven its evolution into a formidable uropathogen with a high potential to spread resistance and virulence traits.