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Malene Winther, André Holdfeldt, Martina Sundqvist, Zahra Rajabkhani, Michael Gabl, Johan Bylund, Claes Dahlgren, Huamei Forsman
A pepducin is a lipopeptide containing a peptide sequence that is identical to one of the intracellular domains of the G-protein coupled receptor (GPCR) assumed to be the target. Neutrophils express two closely related formyl peptide receptors belonging to the family of GPCRs; FPR1 and FPR2 in human and their respective orthologue Fpr1 and Fpr2 in mouse. By applying the pepducin concept, we have earlier identified FPR2 activating pepducins generated from the third intracellular loop of FPR2. The third intracellular loop of FPR2 differs in two amino acids from that of FPR1, seven from Fpr2 and three from Fpr1...
2017: PloS One
Ramalingam Radhakrishnan, Abeer Hashem, Elsayed F Abd Allah
Crop productivity is affected by environmental and genetic factors. Microbes that are beneficial to plants are used to enhance the crop yield and are alternatives to chemical fertilizers and pesticides. Pseudomonas and Bacillus species are the predominant plant growth-promoting bacteria. The spore-forming ability of Bacillus is distinguished from that of Pseudomonas. Members of this genus also survive for a long time under unfavorable environmental conditions. Bacillus spp. secrete several metabolites that trigger plant growth and prevent pathogen infection...
2017: Frontiers in Physiology
Kristine Cannon, Brendan Byrne, Jennifer Happe, Kaiyu Wu, Linda Ward, Laurent Chesnel, Thomas Louie
Objectives: The effects of surotomycin (CB-183,315, MK-4261), a bactericidal cyclic lipopeptide, and vancomycin, the current standard-of-care for Clostridium difficile infection (CDI), on intestinal pathogens and microbiota were evaluated parallel to a Phase 2 randomized, double-blind clinical trial. Methods: The single-centre cohort included 26 patients receiving surotomycin [125 or 250 mg twice daily ( n  =   9 each)] or oral vancomycin [125 mg four times daily ( n  =   8)] for 10 days...
September 12, 2017: Journal of Antimicrobial Chemotherapy
Mengyao Wang, Yue Wu, Yong He, Xiaoxiao Su, Hui Ouyang, Zhifeng Fu
A bioluminescent method was proposed for rapid detection of viable Gram-positive bacteria based on a novel antibiotic-affinity strategy on a magnetic beads (MBs) platform. Daptomycin, a highly efficient lipopeptide antibiotic for Gram-positive bacteria, was used as a recognition agent to functionalize MBs. The daptomycin-functionalized MBs showed high capture and concentration efficiency for Gram-positive bacteria due to the strong binding between daptomycin and bacterial cell membrane in the presence of Ca(2+) ion...
September 22, 2017: Analytica Chimica Acta
Joanna Jammal, Fadia Zaknoon, Amram Mor
We recently reported the aptitude of a membrane-active lipopeptide (C10OOc12O) to sensitize gram-negative bacilli (GNB) to host antibacterial proteins. Here we explored the potential of harnessing such capacity in the presence of antibiotics. For this purpose, we compared Escherichia coli sensitization to antibiotics in broth and plasma; assessed inner and outer membrane damages using scanning electron microscopy, dyes, and mutant strains; and assessed the ability to affect disease course using the mouse peritonitis-sepsis model for mono- and combination therapies...
September 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Xu Cheng, Desalegn W Etalo, Judith E van de Mortel, Ester Dekkers, Linh Nguyen, Marnix H Medema, Jos M Raaijmakers
Pseudomonas fluorescens strain SS101 (Pf.SS101) promotes growth of Arabidopsis thaliana, enhances greening and lateral root formation, and induces systemic resistance (ISR) against the bacterial pathogen Pseudomonas syringae pv. tomato (Pst). Here, targeted and untargeted approaches were adopted to identify bacterial determinants and underlying mechanisms involved in plant growth promotion and ISR by Pf.SS101. Based on targeted analyses, no evidence was found for volatiles, lipopeptides and siderophores in plant growth promotion by Pf...
September 11, 2017: Environmental Microbiology
Kai Schulze, Thomas Ebensen, Saranya Chandrudu, Mariusz Skwarczynski, Istvan Toth, Colleen Olive, Carlos A Guzman
Despite the broad knowledge about the pathogenicity of Streptococcus pyogenes there is still a controversy about the correlate of protection in GAS infections. We aimed in further improving the immune responses stimulated against GAS comparing different vaccine formulations including bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) and BPPCysMPEG, a derivative of the macrophage-activating lipopeptide (MALP-2), as adjuvants, respectively, to be administered with and without the universal T helper cell epitope P25 along with the optimized B cell epitope J14 of the M protein and B and T cell epitopes of SfbI...
September 5, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
Jonathan R Coronel, Ana Marqués, Ángeles Manresa, Francisco J Aranda, José A Teruel, Antonio Ortiz
Lichenysins produced by Bacillus licheniformis are anionic lipopeptide biosurfactants with cytotoxic, antimicrobial, and hemolytic activities that possess enormous potential for chemical and biological applications. Through the use of physical techniques such as differential scanning calorimetry, small- and wide-angle X-ray diffraction, and Fourier-transform infrared spectroscopy as well as molecular dynamics simulations, we report on the interaction of Lichenysin with synthetic phosphatidylcholines differing in hydrocarbon chain length...
September 8, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
Malene Winther, Claes Dahlgren, Huamei Forsman
The pattern recognition formyl peptide receptors (FPRs) belong to the class of G protein-coupled receptors (GPCRs), the largest group of cell-surface receptors involved in a range of physiological processes and pathologies. The FPRs have regulatory function in the initiation as well as resolution of inflammatory reactions, making them highly interesting as targets for drug development. Recent research in the GPCR/FPR fields has uncovered novel receptor biology concepts, including biased signalling/functional selectivity, allosteric modulation, receptor reactivation and receptor cross-talk...
September 7, 2017: Basic & Clinical Pharmacology & Toxicology
Mathieu Surenaud, Christine Lacabaratz, Gérard Zurawski, Yves Lévy, Jean-Daniel Lelièvre
Development of a safe, effective and globally affordable Human Immunodeficiency Virus strain 1 (HIV-1) vaccine offers the best hope for future control of the HIV-1 pandemic. However, with the exception of the recent RV144 trial, which elicited a modest level of protection against infection, no vaccine candidate has shown efficacy in preventing HIV-1 infection or in controlling virus replication in humans. There is also a great need for a successful immunotherapeutic vaccine since combination antiretroviral therapy (cART) does not eliminate the reservoir of HIV-infected cells...
September 7, 2017: Expert Review of Vaccines
Behnoosh Tajik-Ahmadabad, Anastasios Polyzos, Frances Separovic, Fazel Shabanpoor
Splice-switching antisense oligonucleotides (SSOs) are emerging therapeutics with two SSOs recently approved by the FDA for Duchenne muscular dystrophy and spinal muscular atrophy. SSOs are administered without any delivery vector and require large doses to achieve the therapeutic benefit, primarily due to their poor cellular uptake. Although cell-penetrating peptides (CPP) have shown great potential in delivering SSOs into cells, their capacity as delivery vector is limited. Here we have studied the effect of lipid conjugation on the cell permeability of a known CPP (ApoE)...
August 31, 2017: International Journal of Pharmaceutics
Olfa Frikha-Gargouri, Dorra Ben Abdallah, Ilhem Bhar, Slim Tounsi
This study aimed to improve the screening method for the selection of Bacillus biocontrol agents against crown gall disease. The relationship between the strain biocontrol ability and their in vitro studied traits was investigated to identify the most important factors to be considered for the selection of effective biocontrol agents. In fact, previous selection procedure relying only on in vitro antibacterial activity was shown to be not suitable in some cases. A direct plant-protection strategy was performed to screen the 32 Bacillus biocontrol agent candidates...
2017: Frontiers in Plant Science
Hans Uwe Dahms, Sergey Dobretsov
Marine macroalgae produce a wide variety of biologically-active metabolites that have been developed into commercial products, such as antibiotics, immunosuppressive, anti-inflammatory, cytotoxic agents, and cosmetic products. Many marine algae remain clean over longer periods of time, suggesting their strong antifouling potential. Isolation of biogenic compounds and the determination of their structure could provide leads for the development of environmentally-friendly antifouling paints. Isolated substances with potent antifouling activity belong to fatty acids, lipopeptides, amides, alkaloids, lactones, steroids, terpenoids, and pyrroles...
August 28, 2017: Marine Drugs
Sebastian Götze, Regine Herbst-Irmer, Martin Klapper, Helmar Görls, Kilian R A Schneider, Robert Barnett, Thomas Burks, Ursula Neu, Pierre Stallforth
The class of cyclic lipopeptide natural products consists of compounds with a diverse range of bioactivities. In this study, we elucidated the structure of the cyclic lipopeptide anikasin using X-ray crystallography, analyzed its biosynthetic gene cluster, and investigated its natural role in the interaction between the producer strain Pseudomonas fluorescens HKI0770 and protozoal predators. These results led to the conclusion that anikasin has dual functionality enabling swarming motility and acting as a niche amoebicide, which effectively inhibits the social amoeba Polysphondylium violaceum and protects the producer strain from protozoal grazing...
September 1, 2017: ACS Chemical Biology
Katarzyna E Greber
I studied the possibility of using amino acid-based surfactants as emulsifiers at the same time as preservatives. Fourteen lipopeptides were synthesized employing a solid phase peptide synthesis procedure. All compounds were designed to be positively charged from +1 to +4 and acylated with fatty acid chain-palmitic and miristic. The surface activity of the obtained lipopeptides was tested using a semi-automatic tensiometer to calculate parameters describing the behavior of lipopeptides in the air/water interface...
2017: Journal of Surfactants and Detergents
Jin Zhang, Walter R P Scott, Frank Gabel, Miao Wu, Ruqaiba Desmond, JungHwan Bae, Giuseppe Zaccai, W Russ Algar, Suzana K Straus
Daptomycin, sold under the trade name CUBICIN, is the first lipopeptide antibiotic to be approved for use against Gram-positive organisms, including a number of highly resistant species. Over the last few decades, a number of studies have tried to pinpoint the mechanism of action of daptomycin. These proposed modes of action often have points in common (e.g. the requirement for Ca(2+) and lipid membranes containing a high proportion of phosphatidylglycerol (PG) headgroups), but also points of divergence (e...
August 24, 2017: Biochimica et Biophysica Acta
Nuria Roldan, Jesús Pérez-Gil, Michael R Morrow, Begoña García-Álvarez
Lung surfactant (LS) is an essential system supporting the respiratory function. Cholesterol can be deleterious for LS function, a condition that is reversed by the presence of the lipopeptide SP-C. In this work, the structure of LS-mimicking membranes has been analyzed under the combined effect of SP-C and cholesterol by deuterium NMR and phosphorus NMR and by electron spin resonance. Our results show that SP-C induces phase segregation at 37°C, resulting in an ordered phase with spectral features resembling an interdigitated state enriched in dipalmitoylphosphatidylcholine, a liquid-crystalline bilayer phase, and an extremely mobile phase consistent with small vesicles or micelles...
August 22, 2017: Biophysical Journal
Sushil N Benke, Hirekodathakallu V Thulasiram, Hosahudya N Gopi
Herein we report the potent antimicrobial activity of α,γ-hybrid lipopeptides composed of 1:1 alternating α- and γ-amino acids. Along with their potent antimicrobial activity against various Gram-positive and Gram-negative bacteria, these hybrid lipopeptides were found to be less hemolytic. Studies into the mechanism of action revealed that these short cationic lipopeptides bind and disrupt the bacterial cell membrane. Time-kill kinetics analyses revealed that the potent α,γ-hybrid lipopeptides completely inhibit bacterial growth in less than 20 minutes...
August 18, 2017: ChemMedChem
Jun-Jie Koh, Shuimu Lin, Roger W Beuerman, Shouping Liu
Infectious diseases impose serious public health burdens and continue to be a global public health crisis. The treatment of infections caused by multidrug-resistant pathogens is challenging because only a few viable therapeutic options are clinically available. The emergence and risk of drug-resistant superbugs and the dearth of new classes of antibiotics have drawn increasing awareness that we may return to the pre-antibiotic era. To date, lipopeptides have been received considerable attention because of the following properties: They exhibit potent antimicrobial activities against a broad spectrum of pathogens, rapid bactericidal activity and have a different antimicrobial action compared with most of the conventional antibiotics used today and very slow development of drug resistance tendency...
August 19, 2017: Amino Acids
Donyez Frikha Dammak, Ziad Zarai, Soumaya Najah, Rayed Abdennabi, Lassaad Belbahri, Mostafa E Rateb, Hafedh Mejdoub, Sami Maalej
This study has focused on the isolation of twenty-three halophilic actinomycetes from two ponds of different salinity and the evaluation of their ability to exert an antimicrobial activity against both their competitors and several other pathogens. From the 23 isolates, 18 strains showed antagonistic activity, while 19 showed activities against one or more of the seven pathogen strains tested. Six strains exhibited consistent antibacterial activity against Gram-negative and Gram-positive pathogens characterized at the physiological and molecular levels...
2017: BioMed Research International
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