scholarly journals The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from Escherichia coli

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4189
Author(s):  
Aysha B. Mezoughi ◽  
Chiara M. Costanzo ◽  
Gregor M. Parker ◽  
Enas M. Behiry ◽  
Alan Scott ◽  
...  
Keyword(s):  
Binding Constants ◽  
Laboratory Strain ◽  
Glycosidase Inhibitors ◽  
Beta Lactam ◽  
Docking Simulations ◽  
E Coli ◽  
Egg White Lysozyme ◽  
Lytic Transglycosylase ◽  
Lysozyme Inhibitor ◽  
Ic50 Values

Lytic transglycosylases such as Slt35 from E. coli are enzymes involved in bacterial cell wall remodelling and recycling, which represent potential targets for novel antibacterial agents. Here, we investigated a series of known glycosidase inhibitors for their ability to inhibit Slt35. While glycosidase inhibitors such as 1-deoxynojirimycin, castanospermine, thiamet G and miglitol had no effect, the phenothiazinium dye thionine acetate was found to be a weak inhibitor. IC50 values and binding constants for thionine acetate were similar for Slt35 and the hen egg white lysozyme. Molecular docking simulations suggest that thionine binds to the active site of both Slt35 and lysozyme, although it does not make direct interactions with the side-chain of the catalytic Asp and Glu residues as might be expected based on other inhibitors. Thionine acetate also increased the potency of the beta-lactam antibiotic ampicillin against a laboratory strain of E. coli.

Beta-Glucuronidase Inhibition by Constituents of Mulberry Bark

Planta Medica ◽  
2021 ◽  
Author(s):  
Yue Bai ◽  
Lu Chen ◽  
Yun-Feng Cao ◽  
Xu-Dong Hou ◽  
Shou-Ning Jia ◽  
...  
Keyword(s):  
Binding Sites ◽  
Intestinal Bacteria ◽  
Inhibitory Effects ◽  
Glucaric Acid ◽  
Docking Simulations ◽  
E Coli ◽  
Ic50 Values ◽  
Hydrolysis Of ◽  
In Silico Analyses ◽  
Noncompetitive Inhibitors

AbstractIntestinal bacterial β-glucuronidases, the key enzymes responsible for the hydrolysis of various glucuronides into free aglycone, have been recognized as key targets for treating various intestinal diseases. This study aimed to investigate the inhibitory effects and mechanisms of the Mulberry bark constituents on E. coli β-glucuronidase (EcGUS), the most abundant β-glucuronidases produced by intestinal bacteria. The results showed that the flavonoids isolated from Mulberry bark could strongly inhibit E. coli β-glucuronidase, with IC50 values ranging from 1.12 µM to 10.63 µM, which were more potent than D-glucaric acid-1,4-lactone. Furthermore, the mode of inhibition of 5 flavonoids with strong E. coli β-glucuronidase inhibitory activity (IC50 ≤ 5 µM) was carefully investigated by a set of kinetic assays and in silico analyses. The results demonstrated that these flavonoids were noncompetitive inhibitors against E. coli β-glucuronidase-catalyzed 4-nitrophenyl β-D-glucuronide hydrolysis, with Ki values of 0.97 µM, 2.71 µM, 3.74 µM, 3.35 µM, and 4.03 µM for morin (1), sanggenon C (2), kuwanon G (3), sanggenol A (4), and kuwanon C (5), respectively. Additionally, molecular docking simulations showed that all identified flavonoid-type E. coli β-glucuronidase inhibitors could be well-docked into E. coli β-glucuronidase at nonsubstrate binding sites, which were highly consistent with these agentsʼ noncompetitive inhibition mode. Collectively, our findings demonstrated that the flavonoids in Mulberry bark displayed strong E. coli β-glucuronidase inhibition activity, suggesting that Mulberry bark might be a promising dietary supplement for ameliorating β-glucuronidase-mediated intestinal toxicity.

scholarly journals Inhibition of Butyrylcholinesterase and Human Monoamine Oxidase-B by the Coumarin Glycyrol and Liquiritigenin Isolated from Glycyrrhiza uralensis

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3896
Author(s):  
Geum Seok Jeong ◽  
Myung-Gyun Kang ◽  
Joon Yeop Lee ◽  
Sang Ryong Lee ◽  
Daeui Park ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Binding Affinity ◽  
Competitive Inhibitor ◽  
Glycyrrhiza Uralensis ◽  
Form Hydrogen Bond ◽  
Docking Simulations ◽  
Mao B ◽  
Mao A ◽  
Ic50 Values ◽  
Noncompetitive Inhibitor

Eight compounds were isolated from the roots of Glycyrrhiza uralensis and tested for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activities. The coumarin glycyrol (GC) effectively inhibited butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) with IC50 values of 7.22 and 14.77 µM, respectively, and also moderately inhibited MAO-B (29.48 µM). Six of the other seven compounds only weakly inhibited AChE and BChE, whereas liquiritin apioside moderately inhibited AChE (IC50 = 36.68 µM). Liquiritigenin (LG) potently inhibited MAO-B (IC50 = 0.098 µM) and MAO-A (IC50 = 0.27 µM), and liquiritin, a glycoside of LG, weakly inhibited MAO-B (>40 µM). GC was a reversible, noncompetitive inhibitor of BChE with a Ki value of 4.47 µM, and LG was a reversible competitive inhibitor of MAO-B with a Ki value of 0.024 µM. Docking simulations showed that the binding affinity of GC for BChE (−7.8 kcal/mol) was greater than its affinity for AChE (−7.1 kcal/mol), and suggested that GC interacted with BChE at Thr284 and Val288 by hydrogen bonds (distances: 2.42 and 1.92 Å, respectively) beyond the ligand binding site of BChE, but that GC did not form hydrogen bond with AChE. The binding affinity of LG for MAO-B (−8.8 kcal/mol) was greater than its affinity for MAO-A (−7.9 kcal/mol). These findings suggest GC and LG should be considered promising compounds for the treatment of Alzheimer’s disease with multi-targeting activities.

scholarly journals A single amino acid substitution in the Ω-like loop of E. coli PBP5 disrupts its ability to maintain cell shape and intrinsic beta-lactam resistance

Microbiology ◽  
2015 ◽  
Vol 161 (4) ◽  
pp. 895-902 ◽  
Author(s):  
Mouparna Dutta ◽  
Debasish Kar ◽  
Ankita Bansal ◽  
Sandeep Chakraborty ◽  
Anindya S. Ghosh
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Cell Shape ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
Beta Lactam ◽  
E Coli

scholarly journals Ceftobiprole Is Superior to Vancomycin, Daptomycin, and Linezolid for Treatment of Experimental Endocarditis in Rabbits Caused by Methicillin-Resistant Staphylococcus aureus

2009 ◽  
Vol 54 (2) ◽  
pp. 610-613 ◽  
Author(s):  
P. Tattevin ◽  
L. Basuino ◽  
D. Bauer ◽  
B. A. Diep ◽  
H. F. Chambers
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Group ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Rabbit Model ◽  
Laboratory Strain ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
High Affinity

ABSTRACT Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (P < 0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (P < 0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

scholarly journals PREVALENCE OF CEPHALOSPORIN-RESISTANT GRAM-NEGATIVE BACILLI FROM CLINICAL SAMPLES

2016 ◽  
pp. 176
Author(s):  
Kavi Aniis ◽  
Rajamanikandan Kcp ◽  
Arvind Prasanth D
Keyword(s):  
Clinical Samples ◽  
Beta Lactamase ◽  
Bacterial Isolates ◽  
Beta Lactam ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Lactam Ring ◽  
Esbl Producers

<p>ABSTRACT<br />Objective: Beta-lactams are the group of antibiotics that contain a ring called as “beta-lactam ring,” which is responsible for the antibacterial activity.<br />The presence of resistance among Gram-negative organisms is due to the production of beta-lactamases enzymes that hydrolysis the beta-lactam ring<br />thereby conferring resistance to the organism. This study is undertaken to determine the prevalence of extended-spectrum beta-lactamase (ESBL)<br />producing Gram-negative organism from clinical samples.<br />Methods: A total of 112 clinical samples were taken for this study. The combined disc synergistic test (CDST) was used for the phenotypic detection<br />of ESBL producers from the clinical samples. The genotypic identification of ESBL producers was carried out by alkaline lysis method by isolation of<br />plasmid DNA.<br />Result: A total of 87 bacterial isolates were isolated and identified. Among them, Klebsiella (41%) was the predominant organism followed by<br />Escherichia coli (33%), Proteus (10%), Pseudomonas (10%), and Serratia (6%). Among the various bacterial isolates, Klebsiella showed a higher<br />percentage of resistance. The CDST showed that 8 isolates of Klebsiella, 3 isolates of E. coli, and 1 isolate of Pseudomonas were found to be ESBL<br />producers. The genotypic confirmation showed that the two bacterial isolates, namely, Klebsiella and E. coli were found to possess temoniera (TEM)<br />gene which was the 400-500 bp conferring resistance to the antibiotics.<br />Conclusion: The results of this study suggest that early detection of ESBL producing Gram-negative organism is a very important step in planning the<br />therapy of patient in Hospitals. CDST continues to be a good indicator in the detection of ESBL producers.<br />Keywords: Beta-lactamases, Gram-negative bacilli, Extended-spectrum beta-lactamase, Resistance, Combined disc synergistic test.</p><p> </p>

scholarly journals Reclassification of Shigella species as later heterotypic synonyms of Escherichia coli in the Genome Taxonomy Database

2021 ◽  
Author(s):  
Donovan H Parks ◽  
Maria Chuvochina ◽  
Peter R Reeves ◽  
Scott A Beatson ◽  
Philip Hugenholtz
Keyword(s):  
Escherichia Coli ◽  
Type Strain ◽  
Shigella Flexneri ◽  
Laboratory Strain ◽  
Single Species ◽  
Species Definition ◽  
E Coli ◽  
Shigella Species ◽  
K 12 ◽  
Common Laboratory

Members of the genus Shigella have high genomic similarity to Escherichia coli and are often considered to be atypical members of this species. In an attempt to retain Shigella species as recognizable entities, they were reclassified as Escherichia species in the Genome Taxonomy Database (GTDB) using an operational average nucleotide identity (ANI)-based approach nucleated around type strains. This resulted in nearly 80% of E. coli genomes being reclassified to new species including the common laboratory strain E. coli K-12 (to 'E. flexneri') because it is more closely related to the type strain of Shigella flexneri than it is to the type strain of E. coli. Here we resolve this conundrum by treating Shigella species as later heterotypic synonyms of E. coli, present evidence supporting this reclassification, and show that assigning E. coli/Shigella strains to a single species is congruent with the GTDB-adopted genomic species definition.

scholarly journals Bacterial genotypic and patient risk factors for adverse outcomes in Escherichia coli bloodstream infections: a prospective molecular-epidemiological study

2021 ◽  
Author(s):  
Elita Jauneikaite ◽  
Kate Honeyford ◽  
Oliver Blandy ◽  
Mia Mosavie ◽  
Max Pearson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Length Of Stay ◽  
Single Agent ◽  
Bloodstream Infections ◽  
Outcome Data ◽  
Sequence Type ◽  
Adverse Outcomes ◽  
Beta Lactam ◽  
E Coli ◽  
Sequence Types

Background Escherichia coli bloodstream infections have increased rapidly in the UK, for reasons that are unclear. The relevance of highly fit, or multi-drug resistant lineages such as ST131 to overall E. coli disease burden remains to be fully determined. We set out to characterise the prevalence of E. coli multi-locus sequence types (MLST) and determine if these were associated with adverse outcomes in an urban population of E. coli bacteraemia patients. Methods We undertook whole genome sequencing of E. coli blood isolates from all patients with diagnosed E. coli bacteraemia in north-west London from July 2015 to August 2016 and assigned multi-locus sequence types to all isolates. Isolate sequence types were linked to routinely collected antimicrobial susceptibility, patient demographic, and clinical outcome data to explore relationships between the E. coli sequence types, patient factors, and outcomes. Findings A total of 551 E. coli genomes were available for analysis. More than half of these cases were caused by four E. coli sequence types: ST131 (21%), ST73 (15%), ST69 (9%) and ST95 (8%). E. coli genotype ST131-C2 was associated with non-susceptibility to quinolones and third-generation cephalosporins, and also to amoxicillin, augmentin, gentamicin and trimethoprim. An association between the ST131-C2 lineage and longer length-of-stay was detected, although multivariable regression modelling did not demonstrate an association between E. coli sequence type and mortality. However, a number of unexpected associations were identified, including gentamicin non-susceptibility, ethnicity, and sex that might influence mortality and length-of-stay, requiring further research. Interpretation Although E. coli sequence type was associated with antimicrobial non-susceptibility patterns and length-of-stay, we did not find that E. coli sequence type was associated with increased mortality. Where ST131 is prevalent, caution is required when pairing beta-lactam agents with gentamicin or using single agent aminoglycosides.

Comparison of Sensitivity Enterobacteriaceae of Extended Spectrum BetaLactamase (ESBL) against Antibiotics of Quinolone and Carbapenem Group in Clinical Microbiology Laboratory, Faculty of Medicine, Universitas Indonesia

2020 ◽  
Vol 4 (2) ◽  
pp. 71-76
Author(s):  
Conny Riana Tjampakasari ◽  
Alya Iranti ◽  
Tjahjani Mirawati Sudiro
Keyword(s):  
Clinical Microbiology ◽  
Antibiotic Sensitivity ◽  
Female Gender ◽  
Clinical Microbiology Laboratory ◽  
Microbiology Laboratory ◽  
Beta Lactam ◽  
Medical Problems ◽  
E Coli ◽  
Beta Lactam Antibiotics ◽  
Age Range

Antibiotic resistance is a challenge in medical problems. One prevalence of resistance that tends to expand globally is against ESBL-producing Enterobacteriaceae, a group of bacteria capable of destroying beta-lactam antibiotics. The known ESBL producing bacteria are E. coli and K. pneumoniae. This study aims to compare the sensitivity of quinolone and carbapenem antibiotics to ESBL-producing bacteria based on data obtained from Clinical Microbiology Laboratory, Faculty of Medicine, Universitas Indonesia through 2018-2019. Using the Vitek 2® Compact identification method, the results showed that the prevalence of E. coli and K. pneumoniae ESBL was positive less than 5%. All of the ESBL–producing E. coli came from urine specimens, while ESBLproducing K. pneumoniae came from different types of specimens which are sputum and blood. Most prevalence comes in the age range >50 years with female gender. In general, antibiotic sensitivity to the quinolones was less than 50% against ESBL-producing E. coli. Meanwhile, the sensitivity of carbapenem antibiotics reached 100% both against ESBL-producing E.coli and K.pneumoniae.

scholarly journals Ib-M6 Antimicrobial Peptide: Antibacterial Activity against Clinical Isolates of Escherichia coli and Molecular Docking

Antibiotics ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 79 ◽  
Author(s):  
J. M. Flórez-Castillo ◽  
P. Rondón-Villareal ◽  
J. L. Ropero-Vega ◽  
S. Y. Mendoza-Espinel ◽  
J. A. Moreno-Amézquita ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibacterial Activity ◽  
Molecular Docking ◽  
Outer Membrane ◽  
Docking Simulations ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Membrane Components ◽  
K 12 ◽  
Susceptibility Assay

The Ib-M6 peptide has antibacterial activity against non-pathogenic Escherichia coli K-12 strain. The first part of this study determines the antibacterial activity of Ib-M6 against fourteen pathogenic strains of E. coli O157:H7. Susceptibility assay showed that Ib-M6 had values of Minimum Inhibitory Concentration (MIC) lower than streptomycin, used as a reference antibiotic. Moreover, to predict the possible interaction between Ib-M6 and outer membrane components of E. coli, we used molecular docking simulations where FhuA protein and its complex with Lipopolysaccharide (LPS–FhuA) were used as targets of the peptide. FhuA/Ib-M6 complexes had energy values between −39.5 and −40.5 Rosetta Energy Units (REU) and only one hydrogen bond. In contrast, complexes between LPS–FhuA and Ib-M6 displayed energy values between −25.6 and −40.6 REU, and the presence of five possible hydrogen bonds. Hence, the antimicrobial activity of Ib-M6 peptide shown in the experimental assays could be caused by its interaction with the outer membrane of E. coli.

scholarly journals Survey and Sequence Characterization of Bovine Mastitis-Associated Escherichia coli in Dairy Herds

2020 ◽  
Vol 7 ◽  
Author(s):  
John I. Alawneh ◽  
Ben Vezina ◽  
Hena R. Ramay ◽  
Hulayyil Al-Harbi ◽  
Ameh S. James ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Bovine Mastitis ◽  
Antibiotic Resistance Genes ◽  
Tetracycline Resistance ◽  
Sequence Type ◽  
Genotypic Differences ◽  
Beta Lactam ◽  
Sequence Characterization ◽  
E Coli

Escherichia coli is frequently associated with mastitis in cattle. “Pathogenic” and “commensal” isolates appear to be genetically similar. With a few exceptions, no notable genotypic differences have been found between commensal and mastitis-associated E. coli. In this study, 24 E. coli strains were isolated from dairy cows with clinical mastitis in three geographic regions of Australia (North Queensland, South Queensland, and Victoria), sequenced, then genomically surveyed. There was no observed relationship between sequence type (ST) and region (p = 0.51). The most common Multi Locus Sequence Type was ST10 (38%), then ST4429 (13%). Pangenomic analysis revealed a soft-core genome of 3,463 genes, including genes associated with antibiotic resistance, chemotaxis, motility, adhesion, biofilm formation, and pili. A total of 36 different plasmids were identified and generally found to have local distributions (p = 0.02). Only 2 plasmids contained antibiotic resistance genes, a p1303_5-like plasmid encoding multidrug-resistance (trimethoprim, quaternary ammonium, beta-lactam, streptomycin, sulfonamide, and kanamycin) from two North Queensland isolates on the same farm, while three Victorian isolates from the same farm contained a pCFSAN004177P_01-like plasmid encoding tetracycline-resistance. This pattern is consistent with a local spread of antibiotic resistance through plasmids of bovine mastitis cases. Notably, co-occurrence of plasmids containing virulence factors/antibiotic resistance with putative mobilization was rare, though the multidrug resistant p1303_5-like plasmid was predicted to be conjugative and is of some concern. This survey has provided greater understanding of antibiotic resistance within E. coli-associated bovine mastitis which will allow greater prediction and improved decision making in disease management.

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