In silico and in vivo studies of truncated forms of flagellin (FliC) of enteroaggregative Escherichia coli fused to FimH from uropathogenic Escherichia coli as a vaccine candidate against urinary tract infections

2014 ◽  
Vol 175 ◽  
pp. 31-37 ◽  
Author(s):  
Nastaran Sadat Savar ◽  
Ali Jahanian-Najafabadi ◽  
Mehdi Mahdavi ◽  
Mohammad Ali Shokrgozar ◽  
Anis Jafari ◽  
...  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sara Hasanzadeh ◽  
Mehri Habibi ◽  
Mohammad Ali Shokrgozar ◽  
Reza Ahangari Cohan ◽  
Khadijeh Ahmadi ◽  
...  

Abstract Uropathogenic Escherichia coli (UPEC) are common pathogens in urinary tract infections (UTIs), which show resistance to antibiotics. Therefore, there is a need for a vaccine to reduce susceptibility to the infection. In the present study, bioinformatics approaches were employed to predict the best B and T-cell epitopes of UPEC virulence proteins to develop a multiepitope vaccine candidate against UPEC. Then, the efficacy of the candidate was studied with and without Freund adjuvant. Using bioinformatics methods, 3 epitope-rich domains of IutA and FimH antigens were selected to construct the fusion. Molecular docking and Molecular dynamics (MD) simulation were employed to investigate in silico interaction between designed vaccine and Toll-like receptor 4 (TLR4). Our results showed that the levels of IgG and IgA antibodies were improved in the serum and mucosal samples of the vaccinated mice, and the IgG responses were maintained for at least 6 months. The fusion protein was also able to enhance the level of cytokines IFN.γ (Th1), IL.4 (Th2), and IL.17. In challenge experiments, all vaccine combinations showed high potency in the protection of the urinary tract even after 6 months post first injection. The present study indicates that the designed candidate is able to evoke strong protective responses which warrant further studies.


2019 ◽  
Vol 19 (3) ◽  
pp. 322-326 ◽  
Author(s):  
Hassan Valadbeigi ◽  
Elham Esmaeeli ◽  
Sobhan Ghafourian ◽  
Abbas Maleki ◽  
Nourkhoda Sadeghifard

Introduction: The aim of the current study was to investigate the prevalence of virulence genes in uropathogenic Escherichia coli (UPEC) isolates in Ilam. Materials and Methods: For this purpose, a total of 80 UPEC isolates were collected for patients with UTIs during a 6 months period. The multiplex polymerase chain reaction (multiplex PCR) was used to detect the papEF, fimH, iucD, hlyA, fyuA, and ompT genes. Results: The prevalence of fimH, papEF, iucD, fyuA, hlyA, hlyA, and ompT genes were 87.5%, 47.5%, 60%, 67.5%, 27.5%, 47.5% and 71.2%, respectively. Among all of the isolates, 27 profiles were obtained. Conclusion: Our findings demonstrated that the most prevalence was found for fimH, and different distribution of virulence genes suggested different ability of pathogenicity.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1348
Author(s):  
Lívia Slobodníková ◽  
Barbora Markusková ◽  
Michal Kajsík ◽  
Michal Andrezál ◽  
Marek Straka ◽  
...  

Urinary tract infections (UTIs) are among the events that most frequently need medical intervention. Uropathogenic Escherichia coli are frequently their causative agents and the infections are sometimes complicated by the presence of polyresistant nosocomial strains. Phage therapy is a tool that has good prospects for the treatment of these infections. In the present study, we isolated and characterized two bacteriophages with broad host specificity against a panel of local uropathogenic E. coli strains and combined them into a phage cocktail. According to genome sequencing, these phages were closely related and belonged to the Tequatrovirus genus. The newly isolated phages showed very good activity on a panel of local clinical E. coli strains from urinary tract infections. In the form of a two-phage cocktail, they were active on E. coli strains belonging to phylogroups B2 and D, with relatively lower activity in B1 and no response in phylogroup A. Our study is a preliminary step toward the establishment of a national phage bank containing local, well-characterized phages with therapeutic potential for patients in Slovakia.


2020 ◽  
Vol 202 (20) ◽  
Author(s):  
Eric C. DiBiasio ◽  
Hilary J. Ranson ◽  
James R. Johnson ◽  
David C. Rowley ◽  
Paul S. Cohen ◽  
...  

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the leading cause of human urinary tract infections (UTIs), and many patients experience recurrent infection after successful antibiotic treatment. The source of recurrent infections may be persistent bacterial reservoirs in vivo that are in a quiescent state and thus are not susceptible to antibiotics. Here, we show that multiple UPEC strains require a quorum to proliferate in vitro with glucose as the carbon source. At low cell density, the bacteria remain viable but enter a quiescent, nonproliferative state. Of the clinical UPEC isolates tested to date, 35% (51/145) enter this quiescent state, including isolates from the recently emerged, multidrug-resistant pandemic lineage ST131 (i.e., strain JJ1886) and isolates from the classic endemic lineage ST73 (i.e., strain CFT073). Moreover, quorum-dependent UPEC quiescence is prevented and reversed by small-molecule proliferants that stimulate colony formation. These proliferation cues include d-amino acid-containing peptidoglycan (PG) tetra- and pentapeptides, as well as high local concentrations of l-lysine and l-methionine. Peptidoglycan fragments originate from the peptidoglycan layer that supports the bacterial cell wall but are released as bacteria grow. These fragments are detected by a variety of organisms, including human cells, other diverse bacteria, and, as we show here for the first time, UPEC. Together, these results show that for UPEC, (i) sensing of PG stem peptide and uptake of l-lysine modulate the quorum-regulated decision to proliferate and (ii) quiescence can be prevented by both intra- and interspecies PG peptide signaling. IMPORTANCE Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs). During pathogenesis, UPEC cells adhere to and infiltrate bladder epithelial cells, where they may form intracellular bacterial communities (IBCs) or enter a nongrowing or slowly growing quiescent state. Here, we show in vitro that UPEC strains at low population density enter a reversible, quiescent state by halting division. Quiescent cells resume proliferation in response to sensing a quorum and detecting external signals, or cues, including peptidoglycan tetra- and pentapeptides.


2014 ◽  
Vol 82 (4) ◽  
pp. 1572-1578 ◽  
Author(s):  
Karen L. Nielsen ◽  
Pia Dynesen ◽  
Preben Larsen ◽  
Lotte Jakobsen ◽  
Paal S. Andersen ◽  
...  

ABSTRACTCathelicidin (LL-37) and human β-defensin 1 (hBD-1) are important components of the innate defense in the urinary tract. The aim of this study was to characterize whether these peptides are important for developing uncomplicatedEscherichia coliurinary tract infections (UTIs). This was investigated by comparing urinary peptide levels of UTI patients during and after infection to those of controls, as well as characterizing the fecal flora of participants with respect to susceptibility to LL-37 andin vivovirulence. Forty-seven UTI patients and 50 controls who had never had a UTI were included. Participants were otherwise healthy, premenopausal, adult women. LL-37 MIC levels were compared for fecalE. coliclones from patients and controls and were also compared based on phylotypes (A, B1, B2, and D).In vivovirulence was investigated in the murine UTI model by use of selected fecal isolates from patients and controls. On average, UTI patients had significantly more LL-37 in urine during infection than postinfection, and patient LL-37 levels postinfection were significantly lower than those of controls. hBD-1 showed similar urine levels for UTI patients and controls. FecalE. coliisolates from controls had higher LL-37 susceptibility than fecal and UTIE. coliisolates from UTI patients.In vivostudies showed a high level of virulence of fecalE. coliisolates from both patients and controls and showed no difference in virulence correlated with the LL-37 MIC level. The results indicate that the concentration of LL-37 in the urinary tract and low susceptibility to LL-37 may increase the likelihood of UTI in a complex interplay between host and pathogen attributes.


2010 ◽  
Vol 2 (02) ◽  
pp. 070-073 ◽  
Author(s):  
K Prabhat Ranjan ◽  
Neelima Ranjan ◽  
Arindam Chakraborty ◽  
D R Arora

ABSTRACT Purpose: To study the occurrence and characterization of Uropathogenic Escherichia coli (UPEC) in cases with urinary tract infections. Materials and Methods: A total of 220 symptomatic cases from urinary tract infections and 50 stool samples from apparently healthy individuals were included. The colonies identified as Escherichia coli were screened for virulence factors, that is, hemolysin, Mannose Resistant and Mannose Sensitive Hemagglutination (MRHA, MSHA), Cell surface hydrophobicity, and Serum resistance. Results: Among the 220 cases 91 (41.36%) were hemolytic, 68 (30.90%) showed MRHA, 58 (26.36%) were cell surface hydrophobicity positive, and 72 (32.72%) were serum-resistant. In 50 controls, three (6%) were hemolytic, six (12%) showed MRHA, nine (18%) showed cell surface hydrophobicity, and 12 (24%) were serum-resistant. The difference between cases and controls for hemolysis and MRHA were significant (P<0.001 and P<0.01, respectively). A total of 14 atypical E. coli were isolated from the urine and all showed the presence of one or the other virulence markers. Out of the 18 mucoid E.coli isolated, 10 were serum-resistant. Conclusions: The present study revealed that out of 220 urinary isolates, 151 could be labeled as UPEC.


Sign in / Sign up

Export Citation Format

Share Document