scholarly journals Structure-Guided Design of a Fluorescent Probe for the Visualization of FtsZ in Clinically Important Gram-Positive and Gram-Negative Bacterial Pathogens

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Edgar Ferrer-González ◽  
Junso Fujita ◽  
Takuya Yoshizawa ◽  
Julia M. Nelson ◽  
Alyssa J. Pilch ◽  
...  
Keyword(s):  
Fluorescent Probe ◽  
Antibacterial Agents ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Gram Positive ◽  
Optimal Position ◽  
Gram Negative ◽  
High Affinity ◽  
Ftsz Inhibitors ◽  
The Impact

AbstractAddressing the growing problem of antibiotic resistance requires the development of new drugs with novel antibacterial targets. FtsZ has been identified as an appealing new target for antibacterial agents. Here, we describe the structure-guided design of a new fluorescent probe (BOFP) in which a BODIPY fluorophore has been conjugated to an oxazole-benzamide FtsZ inhibitor. Crystallographic studies have enabled us to identify the optimal position for tethering the fluorophore that facilitates the high-affinity FtsZ binding of BOFP. Fluorescence anisotropy studies demonstrate that BOFP binds the FtsZ proteins from the Gram-positive pathogens Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae with Kd values of 0.6–4.6 µM. Significantly, BOFP binds the FtsZ proteins from the Gram-negative pathogens Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii with an even higher affinity (Kd = 0.2–0.8 µM). Fluorescence microscopy studies reveal that BOFP can effectively label FtsZ in all the above Gram-positive and Gram-negative pathogens. In addition, BOFP is effective at monitoring the impact of non-fluorescent inhibitors on FtsZ localization in these target pathogens. Viewed as a whole, our results highlight the utility of BOFP as a powerful tool for identifying new broad-spectrum FtsZ inhibitors and understanding their mechanisms of action.

Impact of empirical antibiotic regimens on mortality in neutropenic patients with bloodstream infection presenting with septic shock

2021 ◽  
Author(s):  
Mariana Chumbita ◽  
Pedro Puerta-Alcalde ◽  
Carlota Gudiol ◽  
Nicole Garcia-Pouton ◽  
Júlia Laporte-Amargós ◽  
...  
Keyword(s):  
Risk Factors ◽  
Septic Shock ◽  
Kidney Injury ◽  
Bloodstream Infections ◽  
Gram Positive ◽  
Gram Negative ◽  
Neutropenic Patients ◽  
Prospective Cohorts ◽  
Independent Risk Factors ◽  
The Impact

Objectives: We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. Methods: Multicenter retrospective study (2010-2019) of two prospective cohorts comparing BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Results: Of 1563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% vs 15%, p<0.001). Gram-negative bacilli caused 81% of episodes with septic shock; gram-positive cocci, 22%; and Candida species 5%. Inappropriate empirical antibiotic treatment (IEAT) was administered in 17.5% of septic shock episodes. Empirical β-lactam combined with other active antibiotics was associated with the lowest mortality observed. When amikacin was the only active antibiotic, mortality was 90%. Addition of empirical specific gram-positive coverage had no impact on mortality. Mortality was higher when IEAT was administered (76% vs 51%, p=0.002). Age >70 years (OR 2.3, 95% CI 1.2-4.7), IEAT for Candida spp. or gram-negative bacilli (OR 3.8, 1.3-11.1), acute kidney injury (OR 2.6, 1.4-4.9) and amikacin as the only active antibiotic (OR 15.2, 1.7-134.5) were independent risk factors for mortality, while combination of β-lactam and amikacin was protective (OR 0.32, 0.18-0.57). Conclusions: Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active β-lactam and amikacin results in the best outcomes.

Diversity profiling of xenic cultures of Dientamoeba fragilis following systematic antibiotic treatment and prospects for genome sequencing

Parasitology ◽  
2019 ◽  
Vol 147 (1) ◽  
pp. 29-38
Author(s):  
Rory Gough ◽  
Joel Barratt ◽  
Damien Stark ◽  
John Ellis
Keyword(s):  
Antibiotic Treatment ◽  
Genome Sequencing ◽  
Ribosomal Dna ◽  
Bacterial Species ◽  
Nutritional Requirement ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Dientamoeba Fragilis ◽  
The Impact

AbstractThe presence of bacterial DNA in Dientamoeba fragilis DNA extracts from culture poses a substantial challenge to sequencing the D. fragilis genome. However, elimination of bacteria from D. fragilis cultures has proven difficult in the past, presumably due to its dependence on some unknown prokaryote/s. This study explored options for removal of bacteria from D. fragilis cultures and for the generation of genome sequence data from D. fragilis. DNA was extracted from human faecal samples and xenic D. fragilis cultures. Extracts were subjected to 16S ribosomal DNA bacterial diversity profiling. Xenic D. fragilis cultures were then subject to antibiotic treatment regimens that systematically removed bacterial species depending on their membrane structure (Gram-positive or Gram-negative) and aerobic requirements. The impact of these treatments on cultures was assessed by 16S amplicon sequencing. Prior to antibiotic treatment, the cultures were dominated by Gram-negative bacteria. Addition of meropenem to cultures eliminated anaerobic Gram-negative bacteria, but it also led to protozoan death after 5 days incubation. The seeding of meropenem resistant Klebsiella pneumoniae strain KPC-2 into cultures before treatment by meropenem prevented death of D. fragilis cells beyond this 5 day period, suggesting that one or more species of Gram-negative bacteria may be an essential nutritional requirement for D. fragilis. Gram-positive cells were completely eliminated using vancomycin without affecting trophozoite growth. Finally, this study shows that genome sequencing of D. fragilis is feasible following bacterial elimination from cultures as the result of the major advances occurring in bioinformatics. We provide evidence on this fact by successfully sequencing the D. fragilis 28S large ribosomal DNA subunit gene using culture-derived DNA.

scholarly journals Antibacterial Potential of Aloe weloensis (Aloeacea) Leaf Latex against Gram-Positive and Gram-Negative Bacteria Strains

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Yohannes Kelifa Emiru ◽  
Ebrahim Abdela Siraj ◽  
Tekleab Teka Teklehaimanot ◽  
Gedefaw Getnet Amare
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Infections ◽  
Inhibition Zone ◽  
Antibacterial Activities ◽  
Maximum Activity ◽  
New Drugs ◽  
Diffusion Method ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Gram Negative

Objective. To evaluate the antibacterial effects of the leaf latex of Aloe weloensis against infectious bacterial strains. Methods. The leaf latex of A. weloensis at different concentrations (400, 500, and 600 mg/ml) was evaluated for antibacterial activities using the disc diffusion method against some Gram-negative species such as Escherichia coli (ATCC 14700) and Pseudomonas aeruginosa (ATCC 35619) and Gram-positive such as Staphylococcus aureus (ATCC 50080) and Enterococcus fecalis (ATCC 4623). Results. The tested concentrations of the latex ranging between 400 and 600 mg·mL−1 showed significant antibacterial activity against bacterial strain. The highest dose (600 mg/ml) of A. weloensis leaf latex revealed the maximum activity (25.93 ± 0.066 inhibition zone) followed by the dose 500 mg/ml against S. aureus. The lowest antibacterial activity was observed by the concentration 400 mg/ml (5.03 ± 0.03) against E. coli. Conclusion. The results of the present investigation suggest that the leaf latex of A. weloensis can be used as potential leads to discover new drugs to control some bacterial infections.

Waterborne Pathogen Detection Using Raman Spectroscopy

2008 ◽  
Vol 62 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Ashish Tripathi ◽  
Rabih E. Jabbour ◽  
Patrick J. Treado ◽  
Jason H. Neiss ◽  
Matthew P. Nelson ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Laser Power ◽  
Pathogen Detection ◽  
Species Level ◽  
Gram Positive ◽  
Gram Negative ◽  
Waterborne Pathogen ◽  
Water Matrix ◽  
The Impact ◽  
Power Densities

Raman spectroscopy is being evaluated as a candidate technology for waterborne pathogen detection. We have investigated the impact of key experimental and background interference parameters on the bacterial species level identification performance of Raman detection. These parameters include laser-induced photodamage threshold, composition of water matrix, and organism aging in water. The laser-induced photodamage may be minimized by operating a 532 nm continuous wave laser excitation at laser power densities below 2300 W/cm2 for Gram-positive Bacillus atrophaeus (formerly Bacillus globigii, BG) vegetative cells, 2800 W/cm2 for BG spores, and 3500 W/cm2 for Gram-negative E. coli (EC) organisms. In general, Bacillus spore microorganism preparations may be irradiated with higher laser power densities than the equivalent Bacillus vegetative preparations. In order to evaluate the impact of background interference and organism aging, we selected a biomaterials set comprising Gram-positive (anthrax simulants) organisms, Gram-negative (plague simulant) organisms, and proteins (toxin simulants) and constructed a Raman signature classifier that identifies at the species level. Subsequently, we evaluated the impact of tap water and storage time in water (aging) on the classifier performance when characterizing B. thuringiensis spores, BG spores, and EC cell preparations. In general, the measured Raman signatures of biological organisms exhibited minimal spectral variability with respect to the age of a resting suspension and water matrix composition. The observed signature variability did not substantially degrade discrimination performance at the genus and species levels. In addition, Raman chemical imaging spectroscopy was used to distinguish a mixture of BG spores and EC cells at the single cell level.

scholarly journals Synthesis of N'-(7-Chloroquinolin-4-yl)-6-Methyl-2-Oxo-4-Phenyl-1,2,3,4-Tetrahydropyrimidine-5-Carbohydrazide Derivatives as Potent Antibacterial Agents

2015 ◽  
Vol 56 ◽  
pp. 82-90 ◽  
Author(s):  
Manoj N. Bhoi ◽  
Mayuri A. Borad ◽  
Edwin A. Pithawala ◽  
Shweta Modi ◽  
Hitesh D. Patel
Keyword(s):  
Elemental Analysis ◽  
Bacterial Strain ◽  
Antibacterial Agents ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Gram Negative ◽  
Ft Ir

Some novel N'-(7-chloroquinolin-4-yl)-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbohydrazide derivatives were synthesized via three step reactions by convectional method. The structures of all the compounds have been confirmed by FT-IR, NMR, and MASS and by elemental analysis. We have been evaluated it inhibition capacity for various gram positive and gram negative bacterial strain. All compounds were found to be good to excellent active against all four bacterial strains.

Lactoferrin-Thymol Complex for Disinfection of Gram-Positive Staphylococcus aureus and Gram-Negative Escherichia coli

2021 ◽  
Author(s):  
Mi Yan ◽  
Shuyue Dong ◽  
Xue Shen ◽  
Chengwen Lu ◽  
Haiqing Ye ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Food Industry ◽  
Antibacterial Agents ◽  
Environmentally Friendly ◽  
Gram Positive ◽  
Gram Negative ◽  
Human Safety

Seeking all-nature derived antibacterial agents with effective disinfection function, high human safety as well as environmentally-friendly characteristics is highly required in food industry. Herein, we report lactoferrin-thymol (LF-Thy) complex as...

scholarly journals Amphipathic guanidine-embedded glyoxamide-based peptidomimetics as novel antibacterial agents and biofilm disruptors

2017 ◽  
Vol 15 (9) ◽  
pp. 2033-2051 ◽  
Author(s):  
Shashidhar Nizalapur ◽  
Onder Kimyon ◽  
Eugene Yee ◽  
Kitty Ho ◽  
Thomas Berry ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Antibacterial Agents ◽  
Gram Negative Bacteria ◽  
Planktonic Cells ◽  
Gram Positive ◽  
Gram Negative

Novel antibacterial peptidomimetics that inhibit the growth of planktonic cells and reduce biofilm formation in both Gram-positive and Gram-negative bacteria.

scholarly journals Densely Functionalized 2-methylideneazetidines: Evaluation as Antibacterials

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3891
Author(s):  
Giovanni Petrillo ◽  
Cinzia Tavani ◽  
Lara Bianchi ◽  
Alice Benzi ◽  
Maria Maddalena Cavalluzzi ◽  
...  
Keyword(s):  
Antibacterial Agents ◽  
Inhibitory Concentration ◽  
General Procedure ◽  
Eukaryotic Cells ◽  
Gram Negative Bacteria ◽  
Pharmacological Profile ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Structure Activity

Twenty-two novel, variously substituted nitroazetidines were designed as both sulfonamide and urethane vinylogs possibly endowed with antimicrobial activity. The compounds under study were obtained following a general procedure recently developed, starting from 4-nitropentadienoates deriving from a common β-nitrothiophenic precursor. While being devoid of any activity against fungi and Gram-negative bacteria, most of the title compounds performed as potent antibacterial agents on Gram-positive bacteria (E. faecalis and three strains of S. aureus), with the most potent congener being the 1-(4-chlorobenzyl)-3-nitro-4-(p-tolyl)azetidine 22, which displayed potency close to that of norfloxacin, the reference antibiotic (minimum inhibitory concentration values 4 and 1–2 μg/mL, respectively). Since 22 combines a relatively efficient activity against Gram-positive bacteria and a cytotoxicity on eucharyotic cells only at 4-times higher concentrations (inhibiting concentration on 50% of the cultured eukaryotic cells: 36 ± 10 μM, MIC: 8.6 μM), it may be considered as a promising hit compound for the development of a new series of antibacterials selectively active on Gram-positive pathogens. The relatively concise synthetic route described herein, based on widely available starting materials, could feed further structure–activity relationship studies, thus allowing for the fine investigation and optimization of the toxico-pharmacological profile.

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