An anti-infective synthetic peptide with dual antimicrobial and immunomodulatory activities.

Antibiotic-resistant infections are predicted to kill 10 million people per year by 2050, costing the global economy $100 trillion. Therefore, there is an urgent need to develop alternative technologies. We have engineered a synthetic peptide called clavanin-MO, derived from a marine tunicate antimicrobial peptide, which exhibits potent antimicrobial and immunomodulatory properties both in vitro and in vivo.

Bacterial Abscess Formation Is Controlled by the Stringent Stress Response and Can Be Targeted Therapeutically.

Cutaneous abscess infections are difficult to treat with current therapies and alternatives to conventional antibiotics are needed. Understanding the regulatory mechanisms that govern abscess pathology should reveal therapeutic interventions for these recalcitrant infections. Here we demonstrated that the stringent stress response employed by bacteria to cope and adapt to environmental stressors was essential for the formation of lesions, but not bacterial growth, in a methicillin resistant Staphylococcus aureus (MRSA) cutaneous abscess mouse model.

Endosomal pH modulation by peptide-gold nanoparticle hybrids enables potent anti-inflammatory activity in phagocytic immune cells.

Toll-like receptor (TLR) signaling plays a central role in the pathophysiology of many acute and chronic human inflammatory diseases, and pharmacological regulation of TLR responses is anticipated to be beneficial in many inflammatory conditions. Currently there are no specific TLR inhibitors in clinical use. To overcome this challenge, we have developed a nano-based TLR inhibitor (peptide-gold nanoparticle hybrids) that inhibits a broad spectrum of TLR responses.

Anti-biofilm peptides as a new weapon in antimicrobial warfare.

Microorganisms growing in a biofilm state are very resilient in the face of treatment by many antimicrobial agents. Biofilm infections are a significant problem in chronic and long-term infections, including those colonizing medical devices and implants. Anti-biofilm peptides represent a very promising approach to treat biofilm-related infections and have an extraordinary ability to interfere with various stages of the biofilm growth mode.

Highly Preorganized Ligand 1,10-Phenanthroline-2,9-dicarboxylic Acid for the Selective Recovery of Uranium from Seawater in the Presence of Competing Vanadium Species.

Studies of the complexation of new promising ligands with uranyl (UO) and other seawater cations can aid the development of more efficient, selective, and robust sorbents for the recovery of uranium from seawater. In this work, we propose that the ligand design principles based on structural preorganization can be successfully applied to obtain a dramatic enhancement in UO ion binding affinity and selectivity. This concept is exemplified through the investigation of the complexes of UO, VO, and VO with the highly preorganized ligand 1,10-phenanthroline-2,9-dicarboxylic acid (PDA) using a combination of fluorescence and absorbance techniques, along with density functional theory (DFT) calculations.

Depicting how Eucalyptus globulus survives drought: involvement of redox and DNA methylation events.

Eucalyptus globulus Labill. is widely cultivated and used by industry but its productivity is currently restricted by drought events, so research focussing on supporting programs to breed adapted germplasm is needed. In the present work we monitored severity of acute drought stress (7 and 11 days after water withholding) and relief (2h and 3 days after rewatering) by quantifying several biochemical markers of oxidative stress and DNA methylation patterns in leaves.

Do household surveys give a coherent view of disability benefit targeting?: a multisurvey latent variable analysis for the older population in Great Britain.

We compare three major UK surveys, the British Household Panel Survey, Family Resources Survey and the English Longitudinal Study of Ageing, in terms of the picture that they give of the relationship between disability and receipt of the benefit. Using the different disability indicators that are available in each survey, we use a structural equation approach involving a latent concept of disability in which probabilities of receiving attendance allowance depend on disability. Despite major differences in design, once sample composition has been standardized through statistical matching, the surveys deliver similar results for the model of disability and receipt of attendance allowance.

Polymyxin: Alternative Mechanisms of Action and Resistance.

Antibiotic resistance among pathogenic bacteria is an ever-increasing issue worldwide. Unfortunately, very little has been achieved in the pharmaceutical industry to combat this problem. This has led researchers and the medical field to revisit past drugs that were deemed too toxic for clinical use.

Synthesis and Evaluation of Ciprofloxacin-Nitroxide Conjugates as Anti-Biofilm Agents.

As bacterial biofilms are often refractory to conventional antimicrobials, the need for alternative and/or novel strategies for the treatment of biofilm related infections has become of paramount importance. Herein, we report the synthesis of novel hybrid molecules comprised of two different hindered nitroxides linked to the piperazinyl secondary amine of ciprofloxacin via a tertiary amine linker achieved utilising reductive amination. The corresponding methoxyamine derivatives were prepared alongside their radical-containing counterparts as controls.

Experimental and Theoretical Investigation of Multispecies Oral Biofilm Resistance to Chlorhexidine Treatment.

We investigate recovery of multispecies oral biofilms following chlorhexidine gluconate (CHX) and CHX with surface modifiers (CHX-Plus) treatment. Specifically, we examine the percentage of viable bacteria in the biofilms following their exposure to CHX and CHX-Plus for 1, 3, and 10 minutes, respectively. Before antimicrobial treatment, the biofilms are allowed to grow for three weeks.

Structural Studies of a Lipid-Binding Peptide from Tunicate Hemocytes with Anti-Biofilm Activity.

Clavanins is a class of peptides (23aa) histidine-rich, free of post-translational modifications. Clavanins have been studied largely for their ability to disrupt bacterial membranes. In the present study, the interaction of clavanin A with membranes was assessed by dynamic light scattering, zeta potential and permeabilization assays.

Interconnection of post-transcriptional regulation: The RNA-binding protein Hfq is a novel target of the Lon protease in Pseudomonas aeruginosa.

Besides being a major opportunistic human pathogen, Pseudomonas aeruginosa can be found in a wide range of environments. This versatility is linked to complex regulation, which is achieved through the action of transcriptional regulators, and post-transcriptional regulation by intracellular proteases including Lon. Indeed, lon mutants in this species show defects in motility, biofilm formation, pathogenicity and fluoroquinolone resistance.

Characterization of the watercress (Nasturtium officinale R. Br.; Brassicaceae) transcriptome using RNASeq and identification of candidate genes for important phytonutrient traits linked to human health.

Background: Consuming watercress is thought to provide health benefits as a consequence of its phytonutrient composition. However, for watercress there are currently limited genetic resources underpinning breeding efforts for either yield or phytonutritional traits. In this paper, we use RNASeq data from twelve watercress accessions to characterize the transcriptome, perform candidate gene mining and conduct differential expression analysis for two key phytonutritional traits: antioxidant (AO) capacity and glucosinolate (GLS) content.

The immunology of host defence peptides: beyond antimicrobial activity.

Host defence peptides (HDPs) are short, cationic amphipathic peptides with diverse sequences that are produced by various cells and tissues in all complex life forms. HDPs have important roles in the body's response to infection and inflammation. This Review focuses on human HDPs and explores the diverse immunomodulatory effects of HDPs from a systems biology perspective, which highlights the interconnected nature of the effect (or effects) of HDPs on the host.

Antibiofilm Peptides: Potential as Broad-Spectrum Agents.

The treatment of bacterial diseases is facing twin threats, with increasing bacterial antibiotic resistance and relatively few novel compounds or strategies under development or entering the clinic. Bacteria frequently grow on surfaces as biofilm communities encased in a polymeric matrix. The biofilm mode of growth is associated with 65 to 80% of all clinical infections.

Major complications associated with fork-based and screw-based tibial tuberosity advancement implants: 438 cases.

This study reports major complications in a large cohort of dogs following tibial tuberosity advancement using either a fork-based or a screw-based implant system. Four hundred thirty-eight stifles were included in the study and major complications occurred in 51 stifles. Explanatory variables evaluated included implant type and body weight.

A new cryptic cationic antimicrobial peptide from human apolipoprotein E with antibacterial activity and immunomodulatory effects on human cells.

Cationic antimicrobial peptides (AMPs) possess fast and broad-spectrum activity against both Gram-negative and Gram-positive bacteria, as well as fungi. It has become increasingly evident that many AMPs, including those that derive from fragments of host proteins, are multifunctional and able to mediate various immunomodulatory functions and angiogenesis. Among these, synthetic apolipoprotein-derived peptides are safe and well tolerated in humans and have emerged as promising candidates in the treatment of various inflammatory conditions.

Targeting Protein-Protein Interactions in the HIF System.

Animals respond to chronic hypoxia by increasing the levels of a transcription factor known as the hypoxia-inducible factor (HIF). HIF upregulates multiple genes, the products of which work to ameliorate the effects of limited oxygen at cellular and systemic levels. Hypoxia sensing by the HIF system involves hydroxylase-catalysed post-translational modifications of the HIF α-subunits, which 1) signal for degradation of HIF-α and 2) limit binding of HIF to transcriptional coactivator proteins.

Quantifying the binding strength of salicylaldoxime-uranyl complexes relative to competing salicylaldoxime-transition metal ion complexes in aqueous solution: a combined experimental and computational study.

The design of new ligands and investigation of UO2(2+) complexations are an essential aspect of reducing the cost of extracting uranium from seawater, improving the sorption efficiency for uranium and the selectivity for uranium over competing ions (such as the transition metal cations). The binding strengths of salicylaldoxime-UO2(2+) complexes were quantified for the first time and compared with the binding strengths of salicylic acid-UO2(2+) and representative amidoxime-UO2(2+) complexes. We found that the binding strengths of salicylaldoxime-UO2(2+) complexes are ∼2-4 log β2 units greater in magnitude than their corresponding salicylic acid-UO2(2+) and representative amidoxime-UO2(2+) complexes; moreover, the selectivity of salicylaldoxime towards the UO2(2+) cation over competing Cu(2+) and Fe(3+) cations is far greater than those reported for salicylic acid and glutarimidedioxime in the literature.

Tryptic Stability of Synthetic Bactenecin Derivatives Is Determined by the Side Chain Length of Cationic Residues and the Peptide Conformation.

Synthetic bactenecins 1 (HHC-10) and 10 (HHC-36), with excellent activities against bacterial superbugs, display low tryptic stability. To investigate factors influencing this stability, a series of 1/10 derived peptides bearing arginine and lysine analogues with varied methylene chains as well as all-d-isomers were synthesized. Whereas incorporation of d-/l-nonproteinogenic amino acids into the turn-forming peptides did not dramatically affect the antimicrobial activities, the degree of peptide cleavage decreased significantly in peptides with the shortest length of cationic side chain and was influenced by the relative conformational stabilities of the turn structure and the stereoselectivity of tryptic digestion.

Cross-tolerance to biotic and abiotic stresses in plants: a focus on resistance to aphid infestation.

Plants co-evolved with an enormous variety of microbial pathogens and insect herbivores under daily and seasonal variations in abiotic environmental conditions. Hence, plant cells display a high capacity to respond to diverse stresses through a flexible and finely balanced response network that involves components such as reduction-oxidation (redox) signalling pathways, stress hormones and growth regulators, as well as calcium and protein kinase cascades. Biotic and abiotic stress responses use common signals, pathways and triggers leading to cross-tolerance phenomena, whereby exposure to one type of stress can activate plant responses that facilitate tolerance to several different types of stress.

A polyalanine peptide derived from polar fish with anti-infectious activities.

Due to the growing concern about antibiotic-resistant microbial infections, increasing support has been given to new drug discovery programs. A promising alternative to counter bacterial infections includes the antimicrobial peptides (AMPs), which have emerged as model molecules for rational design strategies. Here we focused on the study of Pa-MAP 1.

Identification of Synthetic and Natural Host Defense Peptides with Leishmanicidal Activity.

Leishmaniaparasites are a major public health problem worldwide. Effective treatment of leishmaniasis is hampered by the high incidence of adverse effects to traditional drug therapy and the emergence of resistance to current therapeutics. A vaccine is currently not available.