scholarly journals Novel Group of Leaderless Multipeptide Bacteriocins from Gram-Positive Bacteria

2016 ◽  
Vol 82 (17) ◽  
pp. 5216-5224 ◽  
Author(s):  
Kirill V. Ovchinnikov ◽  
Hai Chi ◽  
Ibrahim Mehmeti ◽  
Helge Holo ◽  
Ingolf F. Nes ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antimicrobial Activity ◽  
Bacterial Resistance ◽  
Raw Milk ◽  
Peptide Sequencing ◽  
Homology Search ◽  
Resistant Bacteria ◽  
Content Type ◽  
New Antibiotics ◽  
Inhibitory Spectrum

ABSTRACTFrom raw milk we found 10Lactococcus garvieaeisolates that produce a new broad-spectrum bacteriocin. Though the isolates were obtained from different farms, they turned out to possess identical inhibitory spectra, fermentation profiles of sugars, and repetitive sequence-based PCR (rep-PCR) DNA patterns, indicating that they produce the same bacteriocin. One of the isolates (L. garvieaeKS1546) was chosen for further assessment. Purification and peptide sequencing combined with genome sequencing revealed that the antimicrobial activity was due to a bacteriocin unit composed of three similar peptides of 32 to 34 amino acids. The three peptides are produced without leader sequences, and their genes are located next to each other in an operon-like structure, adjacent to the genes normally involved in bacteriocin transport (ABC transporter) and self-immunity. The bacteriocin, termed garvicin KS (GarKS), showed sequence homology to four multipeptide bacteriocins in databases: the known staphylococcal aureocin A70, consisting of four peptides, and three unannotated putative multipeptide bacteriocins produced byBacillus cereus. All these multipeptide bacteriocin loci show conserved genetic organization, including being located adjacent to conserved genetic determinants (Cro/cI and integrase) which are normally associated with mobile genetic elements or genome rearrangements. The antimicrobial activity of all multipeptide bacteriocins was confirmed with synthetic peptides, and all were shown to have broad antimicrobial spectra, with GarKS being the most active of them. The inhibitory spectrum of GarKS includes important pathogens belonging to the generaStaphylococcus,Bacillus,Listeria, andEnterococcus.IMPORTANCEBacterial resistance to antibiotics is a very serious global problem. There are no new antibiotics with novel antimicrobial mechanisms in clinical trials. Bacteriocins use antimicrobial mechanisms different from those of antibiotics and can kill antibiotic-resistant bacteria, but the number of bacteriocins with very broad antimicrobial spectra is very small. In this study, we have found and purified a novel three-peptide bacteriocin, garvicin KS. By homology search, we were able to find one known and three novel sequence-related bacteriocins consisting of 3 or 4 peptides. None of the peptides has modified amino acids in its sequence. Thus, the activity of all bacteriocins was confirmed with chemically synthesized peptides. All of them, especially garvicin KS, have very broad antibacterial spectra, thus representing a great potential in antimicrobial applications in the food industry and medicine.

scholarly journals Characterizing the Mechanism of Action of an Ancient Antimicrobial, Manuka Honey, against Pseudomonas aeruginosa Using Modern Transcriptomics

mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Daniel Bouzo ◽  
Nural N. Cokcetin ◽  
Liping Li ◽  
Giulia Ballerin ◽  
Amy L. Bottomley ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Activity ◽  
Mechanism Of Action ◽  
Broad Spectrum ◽  
Bacterial Resistance ◽  
Resistant Bacteria ◽  
Antibiotics Resistance ◽  
Manuka Honey ◽  
Content Type ◽  
Bacterial Membranes

ABSTRACT Manuka honey has broad-spectrum antimicrobial activity, and unlike traditional antibiotics, resistance to its killing effects has not been reported. However, its mechanism of action remains unclear. Here, we investigated the mechanism of action of manuka honey and its key antibacterial components using a transcriptomic approach in a model organism, Pseudomonas aeruginosa. We show that no single component of honey can account for its total antimicrobial action, and that honey affects the expression of genes in the SOS response, oxidative damage, and quorum sensing. Manuka honey uniquely affects genes involved in the explosive cell lysis process and in maintaining the electron transport chain, causing protons to leak across membranes and collapsing the proton motive force, and it induces membrane depolarization and permeabilization in P. aeruginosa. These data indicate that the activity of manuka honey comes from multiple mechanisms of action that do not engender bacterial resistance. IMPORTANCE The threat of antimicrobial resistance to human health has prompted interest in complex, natural products with antimicrobial activity. Honey has been an effective topical wound treatment throughout history, predominantly due to its broad-spectrum antimicrobial activity. Unlike traditional antibiotics, honey-resistant bacteria have not been reported; however, honey remains underutilized in the clinic in part due to a lack of understanding of its mechanism of action. Here, we demonstrate that honey affects multiple processes in bacteria, and this is not explained by its major antibacterial components. Honey also uniquely affects bacterial membranes, and this can be exploited for combination therapy with antibiotics that are otherwise ineffective on their own. We argue that honey should be included as part of the current array of wound treatments due to its effective antibacterial activity that does not promote resistance in bacteria.

Drug-resistant bacterial pathogens in milk and some milk products

2014 ◽  
Vol 44 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Shajuty Marjan ◽  
Kamal Kanta Das ◽  
Saurab Kishore Munshi ◽  
Rashed Noor
Keyword(s):  
Public Health ◽  
Developing Countries ◽  
Pathogenic Bacteria ◽  
Raw Milk ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Biochemical Tests ◽  
Content Type ◽  
Milk Products ◽  
Milk Samples

Purpose – Current study was carried to detect the presence of pathogenic bacteria including the drug-resistant ones from milk and milk products. The paper aims to discuss these issues. Design/methodology/approach – Twenty-six raw milk samples from ten different areas, 28 pasteurized milk samples from 12 different companies and 26 yogurt samples from ten different sources in Dhaka city were microbiologically analyzed through cultural and biochemical identification of the isolates. Drug resistance trait was also determined by the Kirby-Bauer method on Muller-Hinton agar. Findings – Out of 80 samples studied, 74 were found to harbor pathogens within a range of 102-104 cfu/ml, including Escherichia coli, Salmonella spp., Staphylococcus aureus, and Vibrio spp. The study of antibiogram revealed that most of the isolates were resistant against most of the commonly used antibiotics. Research limitations/implications – Employment of only cultural/ biochemical tests excluding the molecular detection of virulence and/or antibiotic resistance genes might stand as a shortfall of the study. Nevertheless, such basic approach of microbiology can make this type of study replicable in the resource poor settings in the other developing countries. Practical implications – Routine detection of drug-resistant bacteria can further unveil the complications in chemotherapy during the endemic food borne diseases. Social implications – The study outcome/knowledge would aid to a better public health management especially in the developing countries. Originality/value – The presence of drug-resistant pathogenic bacteria in most of the tested milk samples poses a great public health threat, especially to the children. Therefore, the study revealed the necessity of maintaining proper hygienic practice and care in handling and processing of milk and milk products.

scholarly journals Membrane Perturbation Action Mode and Structure-Activity Relationships of Protonectin, a Novel Antimicrobial Peptide from the Venom of the Neotropical Social Wasp Agelaia pallipes pallipes

2013 ◽  
Vol 57 (10) ◽  
pp. 4632-4639 ◽  
Author(s):  
Kairong Wang ◽  
Wen Dang ◽  
Jiexi Yan ◽  
Ru Chen ◽  
Xin Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Social Wasp ◽  
Multidrug Resistant ◽  
Structural Features ◽  
Helical Conformation ◽  
Resistant Bacteria ◽  
Content Type ◽  
Natural Analog ◽  
Action Mode

ABSTRACTWith the extensive use of antibiotics, multidrug-resistant bacteria emerge frequently. New antimicrobial agents with novel modes of action are urgently needed. It is now widely accepted that antimicrobial peptides (AMPs) could be promising alternatives to conventional antibiotics. In this study, we aimed to study the antimicrobial activity and mechanism of action of protonectin, a cationic peptide from the venom of the neotropical social waspAgelaia pallipes pallipes. We demonstrated that protonectin exhibits potent antimicrobial activity against a spectrum of bacteria, including multidrug-resistant strains. To further understand this mechanism, the structural features of protonectin and its analogs were studied by circular dichroism (CD). The CD spectra demonstrated that protonectin and its natural analog polybia-CP formed a typical α-helical conformation in the membrane-mimicking environment, while its proline-substituted analog had much lower or even no α-helix conformation. Molecular dynamics simulations indicated that the α-helical conformation in the membrane is required for the exhibition of antibacterial activity. In conclusion, protonectin exhibits potent antimicrobial activity by disruption of the integrity of the bacterial membrane, and its α-helical confirmation in the membrane is essential for this action.

scholarly journals Eurotium Cristatum Postfermentation of Fireweed and Apple Tree Leaf Herbal Teas

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Tatiana A. Efimenko ◽  
Elena F. Shanenko ◽  
Tatiana G. Mukhamedzhanova ◽  
Olga V. Efremenkova ◽  
Yuriy A. Nikolayev ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antimicrobial Activity ◽  
Food Safety ◽  
Phenolic Compounds ◽  
Free Amino ◽  
Apple Tree ◽  
Food Product ◽  
New Antibiotics ◽  
Tree Leaf ◽  
Chamaenerion Angustifolium

Fungi Eurotium spp. are the main biological agents that ferment the leaves of the Camellia sinensis tea bush to form a popular food product, postfermented tea. The fungus E. cristatum, stored in the collection of the Gause Institute of New Antibiotics under the number INA 01267, was isolated and identified from a briquette of Fujian Chinese tea. The species identification was carried out based on morphocultural characteristics and DNA sequencing. This study is aimed at determining the feasibility of making postfermented herbal teas using E. cristatum and to evaluate their quality. Autofermented herbal teas from Chamaenerion angustifolium (fireweed) and Malus domestica (apple tree) served as the starting material for this study. The change in the concentration of phenolic compounds, organic acids, sugars, and free amino acids was observed for herbal teas subjected to postfermentation with E. cristatum INA 01267. It was found that the E. cristatum INA 01267 strain does not have antimicrobial activity and does not form mycotoxins, which is an indicator of food safety.

scholarly journals Altering the solubility of the antibiotic candidate Nisin – a computational study

2020 ◽  
Author(s):  
Preeti Pandey ◽  
Ulrich H.E. Hansmann ◽  
Feng Wang
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Antimicrobial Activity ◽  
Broad Spectrum ◽  
Bacterial Resistance ◽  
Force Fields ◽  
Computational Study ◽  
Food Preservative ◽  
Drug Candidates ◽  
Dynamics Simulations

AbstractThe growing bacterial resistance to available antibiotics makes it necessary to look for new drug candidates. An example is a lanthionine-containing nisin, which has a broad spectrum of antimicrobial activity. While nisin is widely utilized as a food preservative, its poor solubility and low stability at physiological pH hinder its use as an antibiotic. As the solubility of nisin is controlled by the residues of the hinge region, we have performed molecular dynamics simulations of various mutants and studied their effects on nisin’s solubility. These simulations are complicated by the presence of two uncommon residues (dehydroalanine and dehydrobutyrine) in the peptide. The primary goal of the present study is to derive rules for designing new mutants that will be more soluble at physiological pH and, therefore, may serve as a basis for the future antibiotic design. Another aim of our study is to evaluate whether existing force fields can model the solubility of these amino acids accurately, in order to motivate further developments of force fields to account for solubility information.

scholarly journals Phage therapy: awakening a sleeping giant

2017 ◽  
Vol 1 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Dwayne R. Roach ◽  
Laurent Debarbieux
Keyword(s):  
Bacterial Resistance ◽  
Phage Therapy ◽  
Therapeutic Modality ◽  
Resistant Bacteria ◽  
Mammalian Host ◽  
Host Immune Responses ◽  
Therapy Effectiveness ◽  
New Antibiotics ◽  
Key Aspects ◽  
Therapy Strategies

For a century, bacterial viruses called bacteriophages have been exploited as natural antibacterial agents. However, their medicinal potential has not yet been exploited due to readily available and effective antibiotics. After years of extensive use, both properly and improperly, antibiotic-resistant bacteria are becoming more prominent and represent a worldwide public health threat. Most importantly, new antibiotics are not progressing at the same rate as the emergence of resistance. The therapeutic modality of bacteriophages, called phage therapy, offers a clinical option to combat bacteria associated with diseases. Here, we discuss traditional phage therapy approaches, as well as how synthetic biology has allowed for the creation of designer phages for new clinical applications. To implement these technologies, several key aspects and challenges still need to be addressed, such as narrow spectrum, safety, and bacterial resistance. We will summarize our current understanding of how phage treatment elicits mammalian host immune responses, as well bacterial phage resistance development, and the potential impact each will have on phage therapy effectiveness. We conclude by discussing the need for a paradigm shift on how phage therapy strategies are developed.

scholarly journals Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 2

2015 ◽  
Vol 60 (3) ◽  
pp. 1194-1201 ◽  
Author(s):  
G. L. Drusano ◽  
William Hope ◽  
Alasdair MacGowan ◽  
Arnold Louie
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Regulatory Review ◽  
Content Type ◽  
Drug Resistant Bacteria ◽  
Antibiotic Drug ◽  
New Chemical Entities

We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens likePseudomonas aeruginosa,Acinetobacterspp., and multidrug-resistant (MDR)Enterobacteriaceae. These lessons need to be applied to our old drugs as well to preserve them and to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects.

scholarly journals Therapeutic Effect and Mechanisms of the Novel Monosulfactam 0073

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Ying Sun ◽  
Xueyuan Liao ◽  
Zhigang Huang ◽  
Yaliu Xie ◽  
Yanbin Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Serial Passage ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Infection Model ◽  
The Novel ◽  
Gram Negative ◽  
Content Type

ABSTRACT This study aimed to evaluate the antimicrobial activity of the novel monosulfactam 0073 against multidrug-resistant Gram-negative bacteria in vitro and in vivo and to characterize the mechanisms underlying 0073 activity. The in vitro activities of 0073, aztreonam, and the combination with avibactam were assessed by MIC and time-kill assays. The safety of 0073 was evaluated using 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and acute toxicity assays. Murine thigh infection and pneumonia models were employed to define in vivo efficacy. A penicillin-binding protein (PBP) competition assay and confocal microscopy were conducted. The inhibitory action of 0073 against β-lactamases was evaluated by the half-maximal inhibitory concentration (IC50), and resistance development was evaluated via serial passage. The monosulfactam 0073 showed promising antimicrobial activity against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii isolates producing metallo-β-lactamases (MBLs) and serine β-lactamases. In preliminary experiments, compound 0073 exhibited safety both in vitro and in vivo. In the murine thigh infection model and the pneumonia models in which infection was induced by P. aeruginosa and Klebsiella pneumoniae, 0073 significantly reduced the bacterial burden. Compound 0073 targeted several PBPs and exerted inhibitory effects against some serine β-lactamases. Finally, 0073 showed a reduced propensity for resistance selection compared with that of aztreonam. The novel monosulfactam 0073 exhibited increased activity against β-lactamase-producing Gram-negative organisms compared with the activity of aztreonam and showed good safety profiles both in vitro and in vivo. The underlying mechanisms may be attributed to the affinity of 0073 for several PBPs and its inhibitory activity against some serine β-lactamases. These data indicate that 0073 represents a potential treatment for infections caused by β-lactamase-producing multidrug-resistant bacteria.

scholarly journals Structure-Activity Studies and Therapeutic Potential of Host Defense Peptides of Human Thrombin

2011 ◽  
Vol 55 (6) ◽  
pp. 2880-2890 ◽  
Author(s):  
Gopinath Kasetty ◽  
Praveen Papareddy ◽  
Martina Kalle ◽  
Victoria Rydengård ◽  
Matthias Mörgelin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antimicrobial Activity ◽  
Host Defense ◽  
Host Defense Peptides ◽  
Content Type ◽  
Peptide Epitopes ◽  
Structure Activity ◽  
Human Thrombin ◽  
Defense Peptides ◽  
Anti Inflammatory

ABSTRACTPeptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteriaEscherichia coliandPseudomonas aeruginosa, the Gram-positive bacteriumStaphylococcus aureus, and the fungusCandida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock andP. aeruginosasepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

scholarly journals Improved Antibiotic-Impregnated Catheters with Extended-Spectrum Activity against Resistant Bacteria and Fungi

2011 ◽  
Vol 56 (2) ◽  
pp. 935-941 ◽  
Author(s):  
Issam Raad ◽  
Jamal A. Mohamed ◽  
Ruth A. Reitzel ◽  
Ying Jiang ◽  
Sammy Raad ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
First Generation ◽  
Bloodstream Infections ◽  
Resistant Bacteria ◽  
Content Type ◽  
Fungal Organisms ◽  
Colonization Model ◽  
Spectrum Activity ◽  
Generation M ◽  
Bacteria And Fungi

ABSTRACTMinocycline-rifampin-impregnated central venous catheters (M/R CVCs) have been shown to be efficacious in reducing catheter-related bloodstream infections (CRBSI) and inhibiting the biofilm adherence of resistant Gram-positive and Gram-negative pathogens, with the exception ofPseudomonas aeruginosaandCandidaspp. To expand the spectrum of antimicrobial activity, a novel second-generation M/R catheter was developed by adding chlorhexidine (CHX-M/R). CVCs and peripherally inserted central catheters (PICCs) were impregnated with CHX-M/R and compared with first-generation M/R catheters, CHX-silver sulfadiazine-treated CVCs (CHX/SS-CVCs), chlorhexidine-treated PICCs, and uncoated catheters. A biofilm catheter colonization model was used to assess the efficacy of catheters against methicillin-resistantStaphylococcus aureus(MRSA), vancomycin-resistantEnterococcus faecium(VRE),P. aeruginosa,Candida albicans, andCandida glabrata. CHX-M/R-impregnated CVCs were the only antimicrobial catheters that completely inhibited the biofilm colonization of all resistant bacterial and fungal organisms tested at all time intervals, and they were significantly superior to uncoated catheters (allPvalues were ≤0.003). Furthermore, CHX-M/R-coated CVCs had a significantly more effective and prolonged (up to 3 weeks) antimicrobial activity against MRSA andP. aeruginosathan M/R, CHX/SS, and uncoated CVCs (P< 0.0001). Similarly, CHX-M/R-coated PICCs were also superior to M/R-coated and CHX-coated PICCs in preventing biofilms of MRSA, VRE,P. aeruginosa, andCandidaspecies (Pvalue = 0.003 for all). Our study shows that novel CHX-M/R-coated catheters have unique properties in completely inhibiting biofilm colonization of MRSA, VRE,P. aeruginosa, and fungi in a manner superior to that of M/R- and chlorhexidine-treated catheters.

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