scholarly journals Antimicrobial Peptides Display Strong Synergy with Vancomycin Against Vancomycin-Resistant E. faecium, S. aureus, and Wild-Type E. coli

2020 ◽  
Vol 21 (13) ◽  
pp. 4578 ◽  
Author(s):  
Chih-Lung Wu ◽  
Ju-Yun Hsueh ◽  
Bak-Sau Yip ◽  
Ya-Han Chih ◽  
Kuang-Li Peng ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Synergistic Effects ◽  
Synergistic Activity ◽  
Wild Type ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
Minimal Inhibitory Concentrations ◽  
E Coli ◽  
Large Size ◽  
Vancomycin Resistant

There is an urgent and imminent need to develop new antimicrobials to fight against antibiotic-resistant bacterial and fungal strains. In this study, a checkerboard method was used to evaluate the synergistic effects of the antimicrobial peptide P-113 and its bulky non-nature amino acid substituted derivatives with vancomycin against vancomycin-resistant Enterococcus faecium, Staphylococcus aureus, and wild-type Escherichia coli. Boron-dipyrro-methene (BODIPY) labeled vancomycin was used to characterize the interactions between the peptides, vancomycin, and bacterial strains. Moreover, neutralization of antibiotic-induced releasing of lipopolysaccharide (LPS) from E. coli by the peptides was obtained. Among these peptides, Bip-P-113 demonstrated the best minimal inhibitory concentrations (MICs), antibiotics synergism, bacterial membrane permeabilization, and supernatant LPS neutralizing activities against the bacteria studied. These results could help in developing antimicrobial peptides that have synergistic activity with large size glycopeptides such as vancomycin in therapeutic applications.

scholarly journals Potent Activity of Hybrid Arthropod Antimicrobial Peptides Linked by Glycine Spacers

2021 ◽  
Vol 22 (16) ◽  
pp. 8919
Author(s):  
Miray Tonk ◽  
James J. Valdés ◽  
Alejandro Cabezas-Cruz ◽  
Andreas Vilcinskas
Keyword(s):  
Antibacterial Activity ◽  
Antimicrobial Peptides ◽  
Synergistic Effects ◽  
Dung Beetle ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Bacterial Strains ◽  
Hybrid Peptide ◽  
Hybrid Peptides ◽  
Promising Source

Arthropod antimicrobial peptides (AMPs) offer a promising source of new leads to address the declining number of novel antibiotics and the increasing prevalence of multidrug-resistant bacterial pathogens. AMPs with potent activity against Gram-negative bacteria and distinct modes of action have been identified in insects and scorpions, allowing the discovery of AMP combinations with additive and/or synergistic effects. Here, we tested the synergistic activity of two AMPs, from the dung beetle Copris tripartitus (CopA3) and the scorpion Heterometrus petersii (Hp1090), against two strains of Escherichia coli. We also tested the antibacterial activity of two hybrid peptides generated by joining CopA3 and Hp1090 with linkers comprising two (InSco2) or six (InSco6) glycine residues. We found that CopA3 and Hp1090 acted synergistically against both bacterial strains, and the hybrid peptide InSco2 showed more potent bactericidal activity than the parental AMPs or InSco6. Molecular dynamics simulations revealed that the short linker stabilizes an N-terminal 310-helix in the hybrid peptide InSco2. This secondary structure forms from a coil region that interacts with phosphatidylethanolamine in the membrane bilayer model. The highest concentration of the hybrid peptides used in this study was associated with stronger hemolytic activity than equivalent concentrations of the parental AMPs. As observed for CopA3, the increasing concentration of InSco2 was also cytotoxic to BHK-21 cells. We conclude that AMP hybrids linked by glycine spacers display potent antibacterial activity and that the cytotoxic activity can be modulated by adjusting the nature of the linker peptide, thus offering a strategy to produce hybrid peptides as safe replacements or adjuncts for conventional antibiotic therapy.

scholarly journals Boosting Synergistic Effects of Short Antimicrobial Peptides With Conventional Antibiotics Against Resistant Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Chih-Lung Wu ◽  
Kuang-Li Peng ◽  
Bak-Sau Yip ◽  
Ya-Han Chih ◽  
Jya-Wei Cheng
Keyword(s):  
Antimicrobial Peptides ◽  
Synergistic Effects ◽  
Antibacterial Activities ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
C Terminus ◽  
Global Spread ◽  
Synergistic Mechanism ◽  
Conventional Antibiotics

The global spread of antibiotic-resistant infections has meant that there is an urgent need to develop new antimicrobial alternatives. In this study, we developed a strategy to boost and/or synergize the activity of conventional antibiotics by combination with antimicrobial peptides tagged with the bulky non-natural amino acid β-naphthylalanine (Nal) to their N- or C-terminus. A checkerboard method was used to evaluate synergistic effects of the parent peptide and the Nal-tagged peptides. Moreover, boron-dipyrro-methene labeled vancomycin was used to characterize the synergistic mechanism of action between the peptides and vancomycin on the bacterial strains. These Nal-tagged antimicrobial peptides also reduced the antibiotic-induced release of lipopolysaccharide from Gram-negative bacteria by more than 99.95%. Our results demonstrate that Nal-tagged peptides could help in developing antimicrobial peptides that not only have enhanced antibacterial activities but also increase the synergistic effects with conventional antibiotics against antibiotic-resistant bacteria.

Antibacterial Activity of cLFchimera and its Synergistic Potential with Antibiotics against Some Foodborne Pathogens Bacteria

2020 ◽  
Author(s):  
Sahar Roshanak ◽  
Zana Pirkhezranian ◽  
Fakhri Shahidi ◽  
Mohammad hadi Sekhavati
Keyword(s):  
Foodborne Pathogens ◽  
Synergistic Effects ◽  
Salmonella Typhi ◽  
Synergistic Activity ◽  
Bacterial Cells ◽  
Bacterial Strains ◽  
E Coli ◽  
Viable Cells ◽  
Electron Microscopy Analysis ◽  
Microscopy Analysis

Abstract Background: Frequent and unlimited use of antibiotics caused the development of antibiotic resistance by microorganisms. Therefore, there is an argent need to discover novel antibacterial agents or a combination of agents as a safe treatment strategy for various infections. The aim of the present study was to evaluate the synergistic effects of cLFchimera, an antimicrobial peptides (AMPs), and antibiotics on several foodborne bacterial strains. Methods: A checkerboard method was used to determine the synergistic effects of cLFchimera and several antibiotics (Gentamicin, Cefazolin and Ceftazidime) on bacterial strains (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi). Results: The combination of cLFchimera and antibiotics generated a total and partial synergistic interaction for all foodborne bacterial strain used in the present study (FIC= 0.25 to 0.77). In most cases, the effect of peptide and antibiotic synergist on release of cellular content was not different compared to antibiotics when they used alone, but the count of viable cells significantly decreased in combination peptide and antibiotics treatments. Generally, antibacterial dynamics of the combination of peptide and antibiotics showed an increase and stable trend after reaching the peak point for E. coli, P. aeruginosa and S. typhi, respectively. Scanning electron microscopy analysis showed that bacterial cells treated with the combination Gentamycin and cLFchimera were markedly damaged, and most of the outermost layer of the bacterial cells disappeared. Conclusion: Overall, our results may suggest that cLFchimera mediated its synergistic activity independent to antibiotics mode of action by disrupting the cell membrane and intramolecular mechanisms.

scholarly journals Multiresistant Bacteria Isolated from Intestinal Faeces of Farm Animals in Austria

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 466
Author(s):  
Herbert Galler ◽  
Josefa Luxner ◽  
Christian Petternel ◽  
Franz F. Reinthaler ◽  
Juliana Habib ◽  
...  
Keyword(s):  
Meat Products ◽  
Animal Husbandry ◽  
Multidrug Resistant ◽  
Farm Animals ◽  
Resistant Bacteria ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Multiresistant Bacteria ◽  
Vancomycin Resistant

In recent years, antibiotic-resistant bacteria with an impact on human health, such as extended spectrum β-lactamase (ESBL)-containing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), have become more common in food. This is due to the use of antibiotics in animal husbandry, which leads to the promotion of antibiotic resistance and thus also makes food a source of such resistant bacteria. Most studies dealing with this issue usually focus on the animals or processed food products to examine the antibiotic resistant bacteria. This study investigated the intestine as another main habitat besides the skin for multiresistant bacteria. For this purpose, faeces samples were taken directly from the intestines of swine (n = 71) and broiler (n = 100) during the slaughter process and analysed. All samples were from animals fed in Austria and slaughtered in Austrian slaughterhouses for food production. The samples were examined for the presence of ESBL-producing Enterobacteriaceae, MRSA, MRCoNS and VRE. The resistance genes of the isolated bacteria were detected and sequenced by PCR. Phenotypic ESBL-producing Escherichia coli could be isolated in 10% of broiler casings (10 out of 100) and 43.6% of swine casings (31 out of 71). In line with previous studies, the results of this study showed that CTX-M-1 was the dominant ESBL produced by E. coli from swine (n = 25, 83.3%) and SHV-12 from broilers (n = 13, 81.3%). Overall, the frequency of positive samples with multidrug-resistant bacteria was lower than in most comparable studies focusing on meat products.

scholarly journals Microbial Isolates from Vegetable Foreign Bodies Inhaled by Dogs

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Sara Flisi ◽  
Manuel Dall’Aglio ◽  
Costanza Spadini ◽  
Clotilde Silvia Cabassi ◽  
Fausto Quintavalla
Keyword(s):  
Respiratory Tract ◽  
Antibiotic Susceptibility ◽  
Resistant Bacteria ◽  
Upper Respiratory Tract ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Bacteria And Fungi ◽  
Susceptibility Tests ◽  
The Right

Grass-seed inhalation is a common problem in canine patients, in particular during summer months, migrating in upper and lower respiratory tract. Grass awns can harbor bacteria and fungi, causing grass seeds foreign body-related disease (GSFBD). Aim of this study was to investigate the aerobic microbial flora isolated from grass awns extracted from 41 dogs with GSFBD and the antibiotic susceptibility of the isolated bacterial strains. Fifty-four grass awns were localized with diagnostic imaging tests and removed by endoscopy from respiratory tract. The most frequent localizations were in the left nostril and the right hemithorax. Only one grass awn was extracted from each patient except in 7 that had more than one. Bacteriological and mycological cultures, strains identification, and antibiotic susceptibility tests were performed. One or more bacterial strains were isolated from all grass awns. Fungal strains were isolated only in 4 cases. Staphylococcussp. was the most frequent isolate in the upper respiratory tract (36.8%), whileE. coli(24.4%) was the most frequent isolate in the lower tract. Fluoroquinolones and Doxycycline were the most effective antibiotics, while resistance was observed against Gentamicin (>93%), Cefapirin, and Clindamycin (>80%). These data are relevant in relation to the use of these antibiotics in both animals and humans, for the risk of transmission of antibiotic resistant bacteria or resistance genes.

scholarly journals Interactions between Penicillin-Binding Proteins (PBPs) and Two Novel Classes of PBP Inhibitors, Arylalkylidene Rhodanines and Arylalkylidene Iminothiazolidin-4-ones

2004 ◽  
Vol 48 (3) ◽  
pp. 961-969 ◽  
Author(s):  
Astrid Zervosen ◽  
Wei-Ping Lu ◽  
Zhouliang Chen ◽  
Ronald E. White ◽  
Thomas P. Demuth ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Wall ◽  
Cell Wall Synthesis ◽  
Bacterial Strains ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
E Coli ◽  
Peptidoglycan Biosynthesis ◽  
Vancomycin Resistant ◽  
Inhibitory Activities

ABSTRACT Several non-β-lactam compounds were active against various gram-positive and gram-negative bacterial strains. The MICs of arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones were lower than those of ampicillin and cefotaxime for methicillin-resistant Staphylococcus aureus MI339 and vancomycin-resistant Enterococcus faecium EF12. Several compounds were found to inhibit the cell wall synthesis of S. aureus and the last two steps of peptidoglycan biosynthesis catalyzed by ether-treated cells of Escherichia coli or cell wall membrane preparations of Bacillus megaterium. The effects of the arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-one derivatives on E. coli PBP 3 and PBP 5, Streptococcus pneumoniae PBP 2xS (PBP 2x from a penicillin-sensitive strain) and PBP 2xR (PBP 2x from a penicillin-resistant strain), low-affinity PBP 2a of S. aureus, and the Actinomadura sp. strain R39 and Streptomyces sp. strain R61 dd-peptidases were studied. Some of the compounds exhibited inhibitory activities in the 10 to 100 μM concentration range. The inhibition of PBP 2xS by several of them appeared to be noncompetitive. The dissociation constant for the best inhibitor (Ki = 10 μM) was not influenced by the presence of the substrate.

scholarly journals Assessment by Time-Kill Methodology of the Synergistic Effects of Oritavancin in Combination with Other Antimicrobial Agents against Staphylococcus aureus

2008 ◽  
Vol 52 (10) ◽  
pp. 3820-3822 ◽  
Author(s):  
Adam Belley ◽  
Eve Neesham-Grenon ◽  
Francis F. Arhin ◽  
Geoffrey A. McKay ◽  
Thomas R. Parr ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Synergistic Effects ◽  
Clinical Development ◽  
Synergistic Activity ◽  
Gram Positive ◽  
Vancomycin Resistant ◽  
Time Kill

ABSTRACT Oritavancin is a semisynthetic lipoglycopeptide in clinical development for serious gram-positive infections. This study describes the synergistic activity of oritavancin in combination with gentamicin, linezolid, moxifloxacin, or rifampin in time-kill studies against methicillin-susceptible, vancomycin-intermediate, and vancomycin-resistant Staphylococcus aureus.

scholarly journals Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai Zheng ◽  
Chunmei Piao ◽  
Yan Liu ◽  
Xuxia Liu ◽  
Tingting Liu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Gut Microbiota ◽  
Patient Group ◽  
Meta Analysis ◽  
Adenosine Monophosphate ◽  
Primary Hypertension ◽  
Wild Type ◽  
Bacterial Strains ◽  
E Coli ◽  
Almost All

Increasing evidences suggest that the gut microbiota have their contributions to the hypertension, but the metagenomic characteristics and potential regulating mechanisms in primary hypertension patients taking antihypertension drugs are not clear yet. We carried out a metagenomic analysis in 30 primary hypertension patients taking antihypertension medications and eight healthy adults without any medication. We found that bacterial strains from species, such as Bacteroides fragilis, Bacteroides vulgatus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus vestibularis, were highly increased in patients; and these strains were reported to generate glycan, short-chain fatty acid (SCFA) and trimethylamine (TMA) or be opportunistic pathogens. Meanwhile, Dorea longicatena, Eubacterium hallii, Clostridium leptum, Faecalibacterium prausnitzii, and some other strains were greatly decreased in the patient group. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that ortholog groups and pathways related to glycan biosynthesis and multidrug resistance were significantly increased in the patient group, and some of the hub genes related to N-glycan biosynthesis were increased in the patient group, while those related to TMA precursor metabolism and amino acid metabolism both increased and decreased in the patient group. Metabolites tested by untargeted liquid chromatography–mass spectrometry (LC-MS) proved the decrease of acetic acid, choline, betaine, and several amino acids in patients’ fecal samples. Moreover, meta-analysis of recent studies found that almost all patients were taking at least one kind of drugs that were reported to regulate adenosine monophosphate-activated protein kinase (AMPK) pathway, so we further investigated if AMPK regulated the metagenomic changes by using angiotensin II-induced mouse hypertensive model on wild-type and macrophage-specific AMPK-knockout mice. We found that the changes in E. coli and Dorea and glycan biosynthesis-related orthologs and pathways were similar in our cohort and hypertensive wild-type mice but reversed after AMPK knockout. These results suggest that the gut microbiota-derived glycan, SCFA, TMA, and some other metabolites change in medication-taking primary hypertension patients and that medications might promote gut microbiota glycan biosynthesis through activating macrophage-AMPK.

scholarly journals Deep learning regression model for antimicrobial peptide design

2019 ◽  
Author(s):  
Jacob Witten ◽  
Zack Witten
Keyword(s):  
Neural Network ◽  
Antimicrobial Peptides ◽  
Network Architecture ◽  
State Of The Art ◽  
Machine Learning Techniques ◽  
Neural Network Architecture ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Naturally Occurring ◽  
Learning Techniques

AbstractAntimicrobial peptides (AMPs) are naturally occurring or synthetic peptides that show promise for treating antibiotic-resistant pathogens. Machine learning techniques are increasingly used to identify naturally occurring AMPs, but there is a dearth of purely computational methods to design novel effective AMPs, which would speed AMP development. We collected a large database, Giant Repository of AMP Activities (GRAMPA), containing AMP sequences and associated MICs. We designed a convolutional neural network to perform combined classification and regression on peptide sequences to quantitatively predict AMP activity against Escherichia coli. Our predictions outperformed the state of the art at AMP classification and were also effective at regression, for which there were no publicly available comparisons. We then used our model to design novel AMPs and experimentally demonstrated activity of these AMPs against the pathogens E. coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Data, code, and neural network architecture and parameters are available at https://github.com/zswitten/Antimicrobial-Peptides.

scholarly journals Chemical Composition and Antimicrobial Activities of Essential Oils of Four Lines of Origanum Vulgare Subsp. Hirtum (Link) Ietswaart Grown in Hungary

2007 ◽  
Vol 2 (11) ◽  
pp. 1934578X0700201 ◽  
Author(s):  
Katalin Veres ◽  
Erzsébet Varga ◽  
Zsuzsanna Schelz ◽  
József Molnár ◽  
Jenő Bernáth ◽  
...  
Keyword(s):  
Essential Oils ◽  
Staphylococcus Epidermidis ◽  
Antimicrobial Activities ◽  
Deficient Mutant ◽  
Wild Type ◽  
Bacterial Strains ◽  
Origanum Vulgare ◽  
Gram Negative ◽  
E Coli ◽  
Yeast Strains

The essential oils of four lines of Origanum vulgare L. subsp. hirtum (Link) Ietswaart cultivated in Hungary were analysed by GC and GC-MS methods. These oils were found to contain carvacrol, γ-terpinene and p-cymene as main constituents. The antimicrobial activities of the various oils and their authentic individual components were tested on Gram-positive and Gram-negative bacterial strains, two Saccharomyces cerevisiae strains and two Candida albicans strains. No difference in sensitivity was found between Escherichia coli, Staphylococcus epidermidis and the yeast strains tested, but there were marked differences in sensitivity between the proton pump-deficient mutant of E. coli and its wild type as regards the growth inhibition and MIC values.

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