scholarly journals Broad-Spectrum and Gram-Negative-Targeting Antibiotics Differentially Regulate Antibody Isotype Responses to Injected Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1240
Author(s):  
Aklilu F. Haile ◽  
Rachel M. Woodfint ◽  
Eunsoo Kim ◽  
Marisa R. Joldrichsen ◽  
Nega Berhe ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antibody Isotype ◽  
Peripheral Tissues ◽  
Gram Negative ◽  
E Coli ◽  
Antibiotic Cocktail ◽  
Mucosal Antibody ◽  
Serum Iga ◽  
Vaccine Antigens ◽  
Iga Antibody

Antibiotics are extensively used worldwide for the treatment of common infections by agents such as E. coli and Salmonella. They also represent the most common cause of alteration of the microbiota in people. We addressed whether broad-spectrum and Gram-negative-targeting antibiotics differentially regulate systemic and mucosal immune responses to vaccines. Antibiotics treatment enhances serum IgG1 responses in mice immunized systemically with a model polyvalent vaccine. This increase was not seen for other IgG subclasses and was dependent on the immunogenicity of vaccine antigens. The broad-spectrum antibiotic cocktail also enhanced serum IgA responses. Interestingly, both the broad spectrum and the antibiotic targeting Gram-negative bacteria enhanced the number of IgA antibody secreting cells in the intestinal lamina propria. This effect was unlikely to be due to an increase in cells expressing gut-homing receptors (i.e., CCR9 and α4β7) in peripheral tissues. On the other hand, the microbiome in mice treated with antibiotics was characterized by an overall reduction of the number of firmicutes. Furthermore, Bacteroidetes were increased by either treatment, and Proteobacteria were increased by the broad-spectrum antibiotics cocktail. Thus, immunoglobulin isotype and subclass responses are differentially regulated by oral antibiotics treatment and the gut microbiota shapes mucosal antibody responses after systemic immunization.

EFFECTS OF PENICILLIN AND BROAD-SPECTRUM ANTIBIOTICS ON THE EMERGENCE OF A GRAM-NEGATIVE BACILLARY FLORA IN THE UPPER RESPIRATORY TRACT OF INFANTS

PEDIATRICS ◽  
1952 ◽  
Vol 9 (5) ◽  
pp. 572-576
Author(s):  
ROBERT S. MCCURDY ◽  
ERWIN NETER
Keyword(s):  
Respiratory Tract ◽  
Broad Spectrum ◽  
Clinical Manifestations ◽  
Upper Respiratory Tract ◽  
Broad Spectrum Antibiotic ◽  
Gram Negative ◽  
E Coli ◽  
Broad Spectrum Antibiotics ◽  
Upper Respiratory ◽  
Aerobic Flora

A study was undertaken on 107 infants to determine the effect of penicillin and broad-spectrum antibiotics (aureomycin, chloromycetin and terramycin), alone and in combination, on the emergence of a predominant gram-negative, bacillary flora of the upper respiratory tract. The following data were obtained: 1. Such a change of the flora took place in 4 out of 12 patients treated with penicillin, 15 out of 22 treated with penicillin and a broad-spectrum antibiotic, and in only 4 out of 21 infants who received a broad-spectrum antibiotic exclusively. 2. Of the 32 cases whose flora had thus changed, members of the E. coli-A. aerogenes group were found in 30 instances, members of the genus Proteus in 3; Ps. aeruginosa in 2; Paracolobactrum in 1; and combinations thereof in four cases. 3. This change of the flora took place in 18 out of 71 infants suffering from respiratory infection and in 14 out of 36 children suffering from other diseases. 4. Reappearance of clinical manifestations was observed in 6 out of 19 patients whose respiratory tract flora changed following the use of penicillin and in none of the four individuals who were treated with a broad-spectrum antibiotic alone. In view of the small number of cases this observation requires confirmation. 5. It is concluded that in infants the use of penicillin used in conjunction with a broad-spectrum antibiotic is followed rather frequently by the emergence in the upper respiratory tract of a predominant gram-negative, bacillary, aerobic flora; such a change occurs less frequently after the use of a broad-spectrum antibiotic alone. The clinical significance of these data is discussed.

scholarly journals Improved broad-spectrum antibiotics against Gram-negative pathogens via darobactin biosynthetic pathway engineering

2021 ◽  
Author(s):  
Sebastian Groß ◽  
Fabian Panter ◽  
Domen Pogorevc ◽  
Carsten E. Seyfert ◽  
Selina Deckarm ◽  
...  
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Broad Spectrum ◽  
Biosynthetic Pathway ◽  
Pathway Engineering ◽  
Gene Deletions ◽  
Gram Negative ◽  
E Coli ◽  
Broad Spectrum Antibiotics

Heterologous expression of a synthetically engineered darobactin gene cluster in E. coli yields new darobactin derivatives with improved anti-Gram-negative activity. Targeted gene deletions provide first insights into biosynthetic steps.

scholarly journals Potent Broad-Spectrum Antibacterial Activity of Amphiphilic Peptides against Multidrug-Resistant Bacteria

2020 ◽  
Vol 8 (9) ◽  
pp. 1398 ◽  
Author(s):  
Yuan Liu ◽  
Jingru Shi ◽  
Ziwen Tong ◽  
Yuqian Jia ◽  
Kangni Yang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antibacterial Activity ◽  
Broad Spectrum ◽  
Multidrug Resistant ◽  
Drug Candidate ◽  
Resistant Bacteria ◽  
Dependent Manner ◽  
Gram Negative ◽  
E Coli ◽  
Amphiphilic Peptide

The emergence and prevalence of multidrug-resistant (MDR) bacteria particularly Gram-negative bacteria presents a global crisis for human health. Colistin and tigecycline were recognized as the last resort of defenses against MDR Gram-negative pathogens. However, the emergence and prevalence of MCR or Tet(X)-mediated acquired drug resistance drastically impaired their clinical efficacy. It has been suggested that antimicrobial peptides might act a crucial role in combating antibiotic resistant bacteria owing to their multiple modes of action and characteristics that are not prone to developing drug resistance. Herein, we report a safe and stable tryptophan-rich amphiphilic peptide termed WRK-12 with broad-spectrum antibacterial activity against various MDR bacteria, including MRSA, colistin and tigecycline-resistant Escherichia coli. Mechanistical studies showed that WRK-12 killed resistant E. coli through permeabilizing the bacterial membrane, dissipating membrane potential and triggering the production of reactive oxygen species (ROS). Meanwhile, WRK-12 significantly inhibited the formation of an E. coli biofilm in a dose-dependent manner. These findings revealed that amphiphilic peptide WRK-12 is a promising drug candidate in the fight against MDR bacteria.

scholarly journals BioSAXS measurements reveal that two antimicrobial peptides induce similar molecular changes in Gram-negative and Gram-positive bacteria

2019 ◽  
Author(s):  
A.R. von Gundlach ◽  
M. Ashby ◽  
J. Gani ◽  
P. M. Lopez-Perez ◽  
A. Cookson ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Mode Of Action ◽  
Bacterial Load ◽  
Ultrastructural Changes ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
Gram Positive Bacteria

AbstractTwo highly active short broad-spectrum AMPs (14D and 69D) with unknown mode of action have been investigated in regards to their effect against the Gram-negative bacteriaE. coliand the Gram-positive bacteria methicillin-resistantStaphylococcus aureus(MRSA). Minimal inhibitory concentration (MIC) measurements using a cell density of 108cfu/ml resulted in values between 16 and 32 μg/ml. Time kill experiments using 108cfu/ml revealed complete killing, except for 69D in combination with MRSA, where bacterial load was reduced a million times. Small angle X-ray scattering of biological samples (BioSAXS) at 108cfu/ml was applied to investigate the ultrastructural changes inE. coliand MRSA in response to these two broad-spectrum AMPs. In addition, electron microscopy (EM) was performed to visualize the treated and non-treated bacteria. As expected, the scattering curves generated using BioSAXS show the ultrastructure of the Gram-positive and Gram-negative bacteria to be very different (BioSAXS is not susceptible to the outer shape). After treatment with either peptide, the scattering curves ofE. coliand MRSA cells are much more alike. This data in conjunction with the EM indicates that ribosomes might be effected by the treatment as well as changes in the nucleoid occurs. Whereas in EM it is notoriously difficult to observe changes for spherical Gram-positives, the BioSAXS results are superior and reveal strongly similar effects for both peptides induced in Gram-positive as well as Gram-negative bacteria. Given the high-throughput possibility and robust statistics BioSAXS can support and speed up mode of action research in AMPs and other antimicrobial compounds, making a contribution towards the development of urgently needed drugs against resistant bacteria.

scholarly journals Production and Characterization of Novel Board-spectrum Antimicrobial 5-butyl-2-pyridine carboxylic acid from Aspergillus fumigatus nHF-01

2022 ◽  
Author(s):  
Vivekananda Mandal ◽  
Narendra Nath Ghosh ◽  
Prashanta Kumar Mitra ◽  
Sukhendu Mandal ◽  
Vivekananda Mandal
Keyword(s):  
Carboxylic Acid ◽  
Broad Spectrum ◽  
Pathogenic Bacteria ◽  
Synergistic Activity ◽  
Antimicrobial Compound ◽  
Gram Negative ◽  
E Coli ◽  
Pyridine Carboxylic Acid ◽  
Pyridine Carboxylic

Abstract Objectives: The present study aims to report on the production optimization, purification, and characterization of structural and functional attributes of a novel broad-spectrum antibacterial compound produced by Aspergillus fumigatus nHF-01 (GenBank Ac. No. MN190286).Materials and Methods: The culture conditions were optimized by using rigorous culture-set preparation considering various abiotic and biotic factors for a higher amount of antimicrobial production. The produced antimicrobial was solvent extracted and purified by preparative TLC and HPLC methods followed by characterization using UV-Vis, FT-IR, ESI-MS, and 1H-NMR spectroscopy. The MIC and MBC of the antimicrobials were determined against a set of Gram-positive and Gram-negative human pathogenic bacteria. The mode of action on cellular morphology and integrity were determined by LDH and SEM studies. Its biofilm-inhibition properties and synergistic activity with antibiotics were studied. The possible cytotoxic effect on human cell lines was also tested by MTT assay. The putative target site of action was evaluated through in silico molecular docking study. Results: The micro-fungus A. fumigatus nHF-01 produced the maximum antibacterial compound while grown in a combination of 2% MEB (w/v) and 4% YE (w/v) at pH 6.0 and 20 °C temperature with 100 rpm agitation for ten days. The DCM extractable crude compound has a potent growth inhibition against the target human food and topical pathogenic bacteria at a 15 mg/ml concentration and is stable up to 100 °C. The spectroscopic studies confirmed the antimicrobial compound as 5-butyl-2-pyridine carboxylic acid with MIC values from 0.069±0.0034 to 1.12±0.052 mg/ml and from 8.925±0.39 to 17.85±0.78 mg/ml; and MBC values from 8.925±0.40 to 17.85±0.776 mg/ml and from 0.069±0.0034 to 0.139±0.0065 mg/ml against human pathogenic Gram-positive and Gram-negative bacteria, respectively. A concentration of 0.139 and 17.85 mg/ml decreased the viability sharply within 15 min of the incubation period with the gradual increase in LDH activity, indicating a robust bactericidal and lytic mode of action. The time-kill kinetics study shows that at a 17.85 mg/ml dose (i.e. MBC), the compound caused zero viability of E. coli and S. epidermidis cells from the initial log CFU/ml 5.78 after 15 h of treatment. It caused a remarkable change in morphology like the formation of blebbing, notch, rupture of the entire cell walls, and entire dissolution of cell integrity at a concentration of 4 µg/ml and 129 µg/ml. It had cytotoxicity against the tested human lung carcinoma A549 cell line. It showed a notable antibiofilm activity at 20 µg/ml and 4 µg/ml comparable to the standard antibiofilm drug usnic acid 10 µg/ml and 64 µg/ml against E. coli and B. cereus. It had a synergistic activity with streptomycin, whereas ciprofloxacin and vancomycin showed additive effects. It showed the highest binding affinities with Quinol-Fumarate Reductase (1l0v), a respiratory enzyme. Conclusion: Thus, the above findings can be concluded that the strain A. fumigatus nHF-01 produces a novel broad-spectrum antimicrobial compound 5-butyl-2-pyridine carboxylic acid with potent bactericidal activity against human food and topical pathogenic bacteria. This is the first report of such a compound from the A. fumigatus.

SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF 3-FORMYL INDOLE BASED SCHIFF BASES

2018 ◽  
Vol 7 (6) ◽  
Author(s):  
Singh Gurvinder ◽  
Singh Prabhsimran ◽  
Dhawan R. K.
Keyword(s):  
Antimicrobial Activity ◽  
Spectral Analysis ◽  
Schiff Bases ◽  
Antimicrobial Agents ◽  
Biological Evaluation ◽  
Fungal Strain ◽  
Bacterial Strains ◽  
Standard Drug ◽  
Gram Negative ◽  
E Coli

In order to develop new antimicrobial agents, a series of 3-formyl indole based Schiff bases were synthesized by reacting 3-formyl indole(indole-3-carboxaldehyde) with substituted aniline taking ethanol as solvent. The reaction was carried in the presence of small amount of p-toluene sulphonic acid as catalyst.All the synthesized compounds were characterized by IR, 1H-NMR spectral analysis. All the synthesized compounds were evaluated for antimicrobial activity against two gram positive bacterial strains (B. subtilisand S. aureus) and two gram negative bacterial strains (P. aeruginosaand E. coli) and one fungal strain (C. albicans). All the synthesized compounds were found to have moderate to good antimicrobial activity. The  standard drug amoxicillin, fluconazole were used for antimicrobial activity. Among the synthesized compounds, the maximum antimicrobial activity was shown by compounds GS04, GS07, GS08 and GS10.

Disinfection of Fruits with Activated Water

2019 ◽  
Vol 10 ◽  
pp. 1864-1872
Author(s):  
Prof. Teodora P. Popova
Keyword(s):  
Antimicrobial Activity ◽  
Aqueous Solutions ◽  
Antimicrobial Properties ◽  
The Other ◽  
Gram Negative Bacteria ◽  
High Antimicrobial Activity ◽  
Gram Negative ◽  
E Coli ◽  
Number Of Microorganisms ◽  
Lower Effect

The effect of ionized aqueous solutions (anolytes and catholyte) in the processing of fruits (cherries, morellos, and strawberries) for decontamination has been tested. Freshly prepared analytes and catholyte without the addition of salts were used, as well as stored for 7 months anolytes, prepared with 0.5% NaCl and a combination of 0.5% NaCl and 0.5% Na2CO3. The anolyte prepared with a combination of 0.5% NaCl and 0.5% Na2CO3, as well as the anolyte obtained with 0.5% NaCl, exhibit high antimicrobial activity against the surface microflora of strawberries, cherries, and sour cherries. They inactivate E. coli for 15 minutes. The other species of the fam. Enterobacteriaceae were also affected to the maximum extent, as is the total number of microorganisms, especially in cherries and sour cherries. Even stored for 7 months, they largely retain their antimicrobial properties. Anolyte and catholyte, obtained without the addition of salts, showed a lower effect on the total number of microorganisms, but had a significant effect on Gram-negative bacteria, and especially with regard to the sanitary indicative E. coli.

In vitro antibacterial and antibiotic-potentiation activities of five edible plant extracts and mode of action against several MDR Gram-negative phenotypes

2020 ◽  
Vol 4 (1) ◽  
pp. 1-14
Author(s):  
Carine M.N. Ngaffo ◽  
Simplice B. Tankeo ◽  
Michel-Gael F. Guefack ◽  
Brice E. N. Wamba ◽  
Paul Nayim ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Bioactive Compounds ◽  
Plant Extracts ◽  
Theobroma Cacao ◽  
Efflux Pumps ◽  
Phoenix Dactylifera ◽  
Food Plants ◽  
Proton Pumps ◽  
Gram Negative ◽  
E Coli

Abstract Background: Bacterial infections involving the multidrug resistant (MDR) strains are among the top leading causes of death throughout the world. Healthcare system across the globe has been suffering from an extra-ordinary burden in terms of looking for the new and more potent antimicrobial compounds. The aim of the present study was to determine the antibacterial activity of some Cameroonian edible plants (Garcinia lucida bark, Phoenix dactylifera pericarps, Theobroma cacao pod, Solanum macrocarpon leaves and Termitomyces titanicus whole plant) and their antibiotics-potentiation effects against some MDR Gram-negative bacteria phenotypes expressing efflux pumps (Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa and Providencia stuartii strains). Methods: The antibacterial activities of plant extract alone and in combination with usual antibiotics were carried out using the micro-dilution method. The effects of the most active plant extract (Garcinia lucida bark) on H+-ATPase-mediated proton pumps and on bacterial growth kinetic were performed using experimental protocols, while qualitative reference methods were used to highligh the major groups of secondary metabolites present in the extracts. Results: Qualitative phytochemical screening of plant extracts indicated that all analysed secondary metabolites were present in Theobroma cacao and Termitomyces titanicus while one (saponins) of them was absent in Garcinia lucida and Solanum macrocarpon. Only three of them (polyphenols, flavonoids and saponins) were detected in Phoenix dactylifera. Antibacterial essays showed that G. lucida was the most active plant as it inhibited the growth of all studied bacteria with strong activity (MIC<100 µg/mL) against E. coli ATCC8739, significant activity (100≤MIC≤512 µg/mL) against 80% of bacteria and moderate activity (512<MIC≤2048 µg/mL) against E. coli AG100A and E. aerogenes (EA289 and CM64). It was followed by T. cacao and S. macrocarpon extracts which exhibited an antibacterial potential against 95% and 80% of bacterial strains, respectively. These three extracts exhibited a bactericidal effect on a few bacteria. Extracts from T. titanicus and P. dactylifera were less active as they moderately (512<MIC≤2048 µg/mL) inhibited the growth of 35% and 10% of bacteria. All extracts selectively potentiated the activities of all antibiotics with improvement activity factors (IAF) ranging from 2 to 256. G. lucida, T. cacao and S. macrocarpon potentiated the activities of 100%, 89% and 67% of antibiotics respectively against more than 70%, suggesting that they contain bioactive compounds which could be considered as efflux pumps inhibitors. Whereas T. titanicus and P. dactylifera improved the activities of almost 40% and 20% of antibiotics, respectively. This increase of activities also characterizes synergistic effects between antibiotics and these bioactive compounds. G. lucida extract at all tested concentrations, strongly inhibited the growth of bacterial strain E. coli ATCC8739 and exhibited an inhibitory effect on this bacterial H+-ATPase-mediated proton pumps increasing the pH of the medium. Conclusion: The overall results indicated that food plants among which G. lucida, T. cacao and S. macrocarpon could have a benefit interest in combatting resistant types of bacteria. Keywords: Food plants; infectious diseases; MDR bacteria; efflux pumps; antibiotics; secondary metabolites.

Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study

2019 ◽  
Vol 18 (31) ◽  
pp. 2731-2740 ◽  
Author(s):  
Sandeep Tiwari ◽  
Debmalya Barh ◽  
M. Imchen ◽  
Eswar Rao ◽  
Ranjith K. Kumavath ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
In Vitro Study ◽  
Docking Studies ◽  
Acetate Kinase ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Novel Target

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

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