scholarly journals Protection of Mice from Lethal Escherichia coli Infection by Chimeric Human Bactericidal/Permeability-Increasing Protein and Immunoglobulin G1 Fc Gene Delivery

2006 ◽  
Vol 51 (2) ◽  
pp. 724-731 ◽  
Author(s):  
Jindong Chen ◽  
Chengyao Li ◽  
Yuanzhi Guan ◽  
Qingli Kong ◽  
Chen Li ◽  
...  

ABSTRACT To evaluate the potentiality of applying gene therapy to bacterial infections, especially for preventing infection in high-risk patients, we investigated protection of mice from challenge with lethal Escherichia coli infection by adeno-associated virus serotype 2 (AAV2)-mediated gene transfer of a chimeric BPI23-Fcγ1 gene, which consisted of human bactericidal/permeability-increasing protein (BPI) gene encoding the functional N terminus (amino acid residues 1 to 199) of human BPI and an Fcγ1 gene encoding the Fc segment of human immunoglobulin G1. Here we show that the target protein that was expressed and secreted into the serum of the gene-transferred mice demonstrated the activity of a neutralizing endotoxin, killing E. coli and mediating opsonization. After lethal E. coli infection, the count of bacteria and the levels of endotoxin and proinflammatory cytokines in the gene-transferred mice were decreased. The survival rate of BPI23-Fcγ1 gene-transferred mice markedly increased, especially in conjunction with antibiotics. Our data suggest that AAV2-mediated chimeric BPI23-Fcγ1 gene delivery could potentially be used clinically for the protection and treatment of infection with gram-negative bacteria in high-risk individuals.

Nanomaterials ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2535
Author(s):  
Mahmood Barani ◽  
Mahira Zeeshan ◽  
Davood Kalantar-Neyestanaki ◽  
Muhammad Asim Farooq ◽  
Abbas Rahdar ◽  
...  

The exploration of multiplexed bacterial virulence factors is a major problem in the early stages of Escherichia coli infection therapy. Traditional methods for detecting Escherichia coli (E. coli), such as serological experiments, immunoassays, polymerase chain reaction, and isothermal microcalorimetry have some drawbacks. As a result, detecting E. coli in a timely, cost-effective, and sensitive manner is critical for various areas of human safety and health. Intelligent devices based on nanotechnology are paving the way for fast and early detection of E. coli at the point of care. Due to their specific optical, magnetic, and electrical capabilities, nanostructures can play an important role in bacterial sensors. Another one of the applications involved use of nanomaterials in fighting microbial infections, including E. coli mediated infections. Various types of nanomaterials, either used directly as an antibacterial agent such as metallic nanoparticles (NPs) (silver, gold, zinc, etc.), or as a nanocarrier to deliver and target the antibiotic to the E. coli and its infected area. Among different types, polymeric NPs, lipidic nanocarriers, metallic nanocarriers, nanomicelles, nanoemulsion/ nanosuspension, dendrimers, graphene, etc. proved to be effective vehicles to deliver the drug in a controlled fashion at the targeted site with lower off-site drug leakage and side effects.


1988 ◽  
Vol 249 (2) ◽  
pp. 319-326 ◽  
Author(s):  
I A Anton ◽  
J R Coggins

The Escherichia coli aroE gene encoding shikimate dehydrogenase was sequenced. The deduced amino acid sequence was confirmed by N-terminal amino acid sequencing and amino acid analysis of the overproduced protein. The complete polypeptide chain has 272 amino acid residues and has a calculated Mr of 29,380. E. coli shikimate dehydrogenase is homologous to the shikimate dehydrogenase domain of the fungal arom multifunctional enzymes and to the catabolic quinate dehydrogenase of Neurospora crassa.


2020 ◽  
Vol 21 (8) ◽  
pp. 772-776
Author(s):  
Xiao-Pei Peng ◽  
Wei Ding ◽  
Jian-Min Ma ◽  
Jie Zhang ◽  
Jian Sun ◽  
...  

Dietary proteins are linked to the pathogenic Escherichia coli (E. coli) through the intestinal tract, which is the site where both dietary proteins are metabolized and pathogenic E. coli strains play a pathogenic role. Dietary proteins are degraded by enzymes in the intestine lumen and their metabolites are transferred into enterocytes to be further metabolized. Seven diarrheagenic E. coli pathotypes have been identified, and they damage the intestinal epithelium through physical injury and effector proteins, which lead to inhibit the digestibility and absorption of dietary proteins in the intestine tract. But the increased tryptophan (Trp) content in the feed, low-protein diet or milk fractions supplementation is effective in preventing and controlling infections by pathogenic E. coli in the intestine.


Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 597
Author(s):  
Luca Pierantoni ◽  
Laura Andreozzi ◽  
Simone Ambretti ◽  
Arianna Dondi ◽  
Carlotta Biagi ◽  
...  

Urinary tract infections (UTIs) are among the most common bacterial infections in children, and Escherichia coli is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. Given the current increasing rates of antibiotic resistance worldwide, this study aimed to investigate the three-year trend in the resistance rate of E. coli isolated from pediatric urine cultures (UCs) in a metropolitan area of northern Italy. We conducted a retrospective review of E. coli-positive, non-repetitive UCs collected in children aged from 1 month to 14 years, regardless of a diagnosis of UTI, catheter colonization, urine contamination, or asymptomatic bacteriuria. During the study period, the rate of resistance to AMC significantly increased from 17.6% to 40.2% (p < 0.001). Ciprofloxacin doubled its resistance rate from 9.1% to 16.3% (p = 0.007). The prevalence of multidrug-resistant E. coli rose from 3.9% to 9.2% (p = 0.015). The rate of resistance to other considered antibiotics remained stable, as did the prevalence of extended spectrum beta-lactamases and extensively resistant E. coli among isolates. These findings call into question the use of AMC as a first-line therapy for pediatric UTIs in our population, despite the indications of recent Italian guidelines.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)


1989 ◽  
Vol 3 (2) ◽  
pp. 105-112 ◽  
Author(s):  
T. S. Grewal ◽  
P. J. Lowry ◽  
D. Savva

ABSTRACT A large portion of the human pro-opiomelanocortin (POMC) peptide corresponding to amino acid residues 59–241 has been cloned and expressed in Escherichia coli. A 1·0 kb DNA fragment encoding this peptide was cloned into the expression vectors pUC8 and pUR291. Plasmid pJMBG51 (a pUC8 recombinant) was found to direct the expression of a 24 kDa peptide. The recombinant pUR291 (pJMBG52) was shown to produce a β-galactosidase fusion protein of 140 kDa. Western blot analysis showed that both the 24 kDa and 140 kDa peptides are recognized by antibodies raised against POMC-derived peptides. The β-galactosidase fusion protein has been partially purified from crude E. coli cell lysates using affinity chromatography on p-aminobenzyl-1-thio-β-d-galactopyranoside agarose.


2013 ◽  
Vol 454 (3) ◽  
pp. 585-595 ◽  
Author(s):  
Joana Sá-Pessoa ◽  
Sandra Paiva ◽  
David Ribas ◽  
Inês Jesus Silva ◽  
Sandra Cristina Viegas ◽  
...  

In the present paper we describe a new carboxylic acid transporter in Escherichia coli encoded by the gene yaaH. In contrast to what had been described for other YaaH family members, the E. coli transporter is highly specific for acetic acid (a monocarboxylate) and for succinic acid (a dicarboxylate), with affinity constants at pH 6.0 of 1.24±0.13 mM for acetic acid and 1.18±0.10 mM for succinic acid. In glucose-grown cells the ΔyaaH mutant is compromised for the uptake of both labelled acetic and succinic acids. YaaH, together with ActP, described previously as an acetate transporter, affect the use of acetic acid as sole carbon and energy source. Both genes have to be deleted simultaneously to abolish acetate transport. The uptake of acetate and succinate was restored when yaaH was expressed in trans in ΔyaaH ΔactP cells. We also demonstrate the critical role of YaaH amino acid residues Leu131 and Ala164 on the enhanced ability to transport lactate. Owing to its functional role in acetate and succinate uptake we propose its assignment as SatP: the Succinate–Acetate Transporter Protein.


2016 ◽  
Vol 20 (7) ◽  
pp. 1359-1367 ◽  
Author(s):  
Renato Costi ◽  
Matteo De Pastena ◽  
Giuseppe Malleo ◽  
Giovanni Marchegiani ◽  
Giovanni Butturini ◽  
...  

Author(s):  
Mehmet E. Bulut ◽  
Gülen Hürkal ◽  
Nazan Dalgıç

Abstract Objective Antimicrobial resistance poses a serious threat to children's health. In recent years, high-risk Escherichia coli ST131 has become an important target for global surveillance studies. The E.coli ST131 clone is associated with extended spectrum β-lactamase (ESBL) production, as well as multidrug resistance and treatment failure. Studies on this clone in the pediatric age group are limited. We aim to investigate the rate of high-risk E. coli ST131 clone in ESBL-positive E. coli isolates obtained from pediatric patients. Methods A total of 292 ESBL-positive E. coli isolates from clinical samples of pediatric patients was included in the study. MALDI-TOF MS system was used for bacterial identification. Susceptibility tests were performed using BD Phoenix automated system. ST131 detection was done by MALDI-TOF-MS. Fisher's exact test was used to compare the groups (significance <0.05). Results A total of 292 isolates was analyzed. The high-risk ST131 clone was detected in 117 (40%) of the 292 ESBL-positive isolates. ST131 rates were found to be significantly higher in children under the age of 5 years compared with children over the age of 5 years (49.3 vs. 31.1%, p = 0.0019). Ciprofloxacin resistance was higher in ST131 isolates (45.6 vs. 31.7%; p < 0.05). Conclusion The rate of the ST131 clone was found to be high in the pediatric population. The significantly high rate of resistance to ciprofloxacin, which is not commonly used in the pediatric population, in ST131 isolates reveals the importance of the spread of high-risk clones for the development of resistance.


Open Biology ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. 170040 ◽  
Author(s):  
Qianqian Di ◽  
Qing Lin ◽  
Zhibin Huang ◽  
Yali Chi ◽  
Xiaohui Chen ◽  
...  

Neutrophils play important roles in innate immunity and are mainly dependent on various enzyme-containing granules to kill engulfed microorganisms. Zebrafish nephrosin ( npsn ) is specifically expressed in neutrophils; however, its function is largely unknown. Here, we generated an npsn mutant ( npsn smu5 ) via CRISPR/Cas9 to investigate the in vivo function of Npsn. The overall development and number of neutrophils remained unchanged in npsn -deficient mutants, whereas neutrophil antibacterial function was defective. Upon infection with Escherichia coli , the npsn smu5 mutants exhibited a lower survival rate and more severe bacterial burden, as well as augmented inflammatory response to challenge with infection when compared with wild-type embryos, whereas npsn -overexpressing zebrafish exhibited enhanced host defence against E. coli infection. These findings demonstrated that zebrafish Npsn promotes host defence against bacterial infection. Furthermore, our findings suggested that npsn -deficient and -overexpressing zebrafish might serve as effective models of in vivo innate immunity.


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