Each year, 25,000 people die in Europe as a result of antibiotic-resistant infections, costing the European Union >1.5 billion euros. A similar scenario takes place in the United States, where >2 million people are infected with drug-resistant bacteria leading to 23,000 deaths annually. In addition to the increase in bacterial resistance to available antibiotics, no antimicrobials designed to combat these recalcitrant infections have been approved for use in humans.
However, in recent years increasing effort has been devoted to identifying strategies against persistent infections. One such approach is the use of antimicrobial peptides (AMPs) as templates to generate synthetic peptide variants with improved activity. AMPs are evolutionarily conserved.
Formation and development of bacterial biofilms in the food industry could be a cause of food contamination, compromising food safety and shelf-life. Among the factors modulating biofilm formation, this review will focus in conditions normally encountered by bacteria in food environments, especially in biofilm initiation and development. The effect of environmental factors (substratum, temperature, oxygen concentration, hydrodynamic effects, food matrix composition, and microbial interactions) on biofilm formation is multifaceted and, in many circumstances, their influence could be compensatory. A better knowledge of these factors would allow for a better control of biofilm formation, either by avoiding and/or eradicating biofilms or by defining adequate Hazard Analysis and Critical Control Point systems in the food industry.
Antimicrobial peptides (AMPs) have emerged as one of several viable options for treatment of infections caused by multidrug-resistant microorganisms, which continue to pose the single greatest public health challenge to humankind. Unlike conventional antibiotics, AMPs affects several key extracellular and intracellular targets in bacteria simultaneously, drastically limiting chances of drug-resistance development. Over the years it has been possible to manipulate their chemical structures to design novel anti-infectives for the treatment of systemic and topical infections based on detailed information generated from structural-activity studies. These novel synthetic AMPs exhibit enhanced antimicrobial activity, less cytotoxicity to mammalian cells and enhanced stability to proteases. This review discusses some current developments that have expanded our understanding of their diverse killing mechanisms and shows how this has been employed in the design of AMPs with predictable activity.
Natural Antimicrobial peptides (AMPs) are important components of immune systems and possess immuno-modulatory and broad spectrum antimicrobial activities. These host-defense peptides failed to resist protease degradation or to efficiently inhibit biofilm formation. We describe in this review the different strategies to improve AMPs and develop peptides that could be used clinically and in industry through antimicrobial, antibiofilm and/or anti-inflammatory activities, protease resistant property and without being cytotoxic. They can be developed as free molecules or immobilized on surfaces or in synergy with other treatments. AMPs could be the next important step in bacteriology treatment after antibiotic discovery.
This review will focus onstrategies to develop new treatments that target the biofilm mode of growth andthat can be used to treat biofilm infections. These approaches aim to reduce orinhibit biofilm formation, or to increase biofilm dispersion. Many antibiofilmcompounds are not bactericidal but render the cells in a planktonic growthstate, which are more susceptible to antibiotics and more easily cleared by theimmune system. Novel compounds are being developed with antibiofilm activitythat includes antimicrobial peptides, natural products, small molecules andpolymers. Bacteriophages are being considered for use in treating biofilms, aswell as the use of enzymes that degrade the extracellular matrix polymers todissolve biofilms. There is great potential in these new approaches for use intreating chronic biofilm infections.
Angiotensin II acting via Angiotensin II type 2 receptors (AT2Rs) is believed to be protective against increases in blood pressure and affects renal function under pathophysiological conditions. Recently we have observed that stimulation of AT2Rs in obese Zucker rats shifts the balance beween two opposing arms of renin angiotensin system (RAS) i.e. Angiotensin converting enzyme (ACE) Angiotensin II-Angiotensin II type 1 receptor (AT1R) vs ACE2)-Angiotensin-(1-7)-Mas receptor. In the present study, we investigated the role of AT2Rs in regulating Renin Angiotensin System (RAS) components in mice. Kidney cortex from AT2R knockout (AT2RKO) mice and wild type (WT) with similar background (C57BL/6) of 20 weeks of age were used in the study. The cortical ACE2 activity was significantly decreased in AT2RKO mice (41±11, RFU/min) compared to WT (113±8 RFU/min). LC/MS analysis of cortical tissue revealed that Ang-(1-7) was also significantly decreased in AT2RKO mice (WT: 33±5, AT2RKO: 14±02.8 fmoles/mg tissue). Mas receptor expression in the kidney cortex was also significantly decreased to almost 2.5 fold in AT2RKO compared to WT. The ACE concentration (ng ACE/µg tissue) was significantly increased in AT2RKO mice (3±0.4) compared to WT (1.9±0.02). Deletion of AT2R significantly increased AT1R expression to almost two-fold, increased Ang II levels (WT: 31±2.7, AT2RKO: 47±2.7 fmoles/mg tissue) and had no effect on renin activity compared to WT. This study suggests that deletion of AT2R decreases the beneficial component of RAS i.e. ACE2-Ang-(1-7)-MasR and increases the deleterious ACE-Ang II-AT1R axis in mice. Such changes indicate the importance of AT2R in regulating several components of RAS and a potential role in renal function and blood pressure control.
Dissection of organismal metabolomes into smaller subunits of life holds the potential to unravel the details of operative metabolic pathways and metabolic compartmentation at the sub-cellular level. Although metabolomes have been characterized at tissue, cellular, and cell-population types, little efforts have been put towards separation of sub-cellular metabolomes. Obvious challenges in lack of pure preparations of organelles, shared metabolites among them, and complicated metabolic regulations in them has impeded our advances in this domain of metabolomics. However, in the post-genomic era, significant advances have been made in predicting plant protein and transcriptomic localization to subcellular organelles through computational approaches. We summarize the recent efforts and progresses made in directions of understanding the plant sub-cellular (organellar) metabolomes.
Phosphoinositide 3-kinases (PI3Ks) are central regulators of cellular responses to extracellular stimuli, and are involved in growth, proliferation, migration, and metabolism. The Class I PI3Ks are activated by Receptor Tyrosine Kinases (RTKs) or G Protein-Coupled Receptors (GPCRs), and their signaling is commonly deregulated in disease conditions. Among the class I PI3Ks, the p110β isoform is unique in being activated by both RTKs and GPCRs, and its ability to bind Rho-GTPases and Rab5. Recent studies have characterized these p110β interacting partners, defining the binding mechanisms and regulation, and thus provide insight into the function of this kinase in physiology and disease. This review summarizes the developments in p110β research, focusing on the interacting partners and their role in p110β-mediated signaling.
Dragmacidin D, a bis(indole) alkaloid was isolated from deep water marine sponge in 1992 and 1998. The structural feature consists of two unsymmetrically substituted indole moiety connected through a pyrazinone linker and has a polar aminoimidazole moiety. Due to remarkable structural features and diverse biological properties, dragmacidin D has attracted attention from synthetic community. In this review, the syntheses of dragmacidin D for last 13 years are briefly summarized.
Next-generation sequencing (NGS) technologies have greatly reduce the cost and difficulty of sequencing partial genomes. Genome datasets are a promising approach to generate genomic resources to further support population genomic and association genetic studies. In a recent study da Rocha Perini et al. describe the complete chloroplast genome of the endangered Cattleya crispata, the first genome from the Neotropical orchid subtribe Laeliinae. The development of genomic resources of Cattleya species adds to the genomic toolbox for conservation genetics and allows new approaches to better understand the complex evolutionary history of Neotropical orchid species.