The Long-Distance Transport of Some Plant Hormones and Possible Involvement of Lipid-Binding and Transfer Proteins in Hormonal Transport.

Adaptation to changes in the environment depends, in part, on signaling between plant organs to integrate adaptive response at the level of the whole organism. Changes in the delivery of hormones from one organ to another through the vascular system strongly suggest that hormone transport is involved in the transmission of signals over long distances. However, there is evidence that, alternatively, systemic responses may be brought about by other kinds of signals (e.g., hydraulic or electrical) capable of inducing changes in hormone metabolism in distant organs. Long-distance transport of hormones is therefore a matter of debate. This review summarizes arguments for and against the involvement of the long-distance transport of cytokinins in signaling mineral nutrient availability from roots to the shoot. It also assesses the evidence for the role of abscisic acid (ABA) and jasmonates in long-distance signaling of water deficiency and the possibility that Lipid-Binding and Transfer Proteins (LBTPs) facilitate the long-distance transport of hormones. It is assumed that proteins of this type raise the solubility of hydrophobic substances such as ABA and jasmonates in hydrophilic spaces, thereby enabling their movement in solution throughout the plant. This review collates evidence that LBTPs bind to cytokinins, ABA, and jasmonates and that cytokinins, ABA, and LBTPs are present in xylem and phloem sap and co-localize at sites of loading into vascular tissues and at sites of unloading from the phloem. The available evidence indicates a functional interaction between LBTPs and these hormones.

Dimerization of the ß-Hairpin Membrane-Active Cationic Antimicrobial Peptide Capitellacin from Marine Polychaeta: An NMR Structural and Thermodynamic Study.

Capitellacin is the ß-hairpin membrane-active cationic antimicrobial peptide from the marine polychaeta Capitella teleta. Capitellacin exhibits antibacterial activity, including against drug-resistant strains. To gain insight into the mechanism of capitellacin action, we investigated the structure of the peptide in the membrane-mimicking environment of dodecylphosphocholine (DPC) micelles using high-resolution NMR spectroscopy. In DPC solution, two structural forms of capitellacin were observed: a monomeric ß-hairpin was in equilibrium with a dimer formed by the antiparallel association of the N-terminal ß-strands and stabilized by intermonomer hydrogen bonds and Van der Waals interactions. The thermodynamics of the enthalpy-driven dimerization process was studied by varying the temperature and molar ratios of the peptide to detergent. Cooling the peptide/detergent system promoted capitellacin dimerization. Paramagnetic relaxation enhancement induced by lipid-soluble 12-doxylstearate showed that monomeric and dimeric capitellacin interacted with the surface of the micelle and did not penetrate into the micelle interior, which is consistent with the "carpet" mode of membrane activity. An analysis of the known structures of ß-hairpin AMP dimers showed that their dimerization in a membrane-like environment occurs through the association of polar or weakly hydrophobic surfaces. A comparative analysis of the physicochemical properties of ß-hairpin AMPs revealed that dimer stability and hemolytic activity are positively correlated with surface hydrophobicity. An additional positive correlation was observed between hemolytic activity and AMP charge. The data obtained allowed for the provision of a more accurate description of the mechanism of the oligomerization of ß-structural peptides in biological membranes.

Novel BRICHOS-Related Antimicrobial Peptides from the Marine Worm Heteromastus filiformis: Transcriptome Mining, Synthesis, Biological Activities, and Therapeutic Potential.

Marine polychaetes represent an extremely rich and underexplored source of novel families of antimicrobial peptides (AMPs). The rapid development of next generation sequencing technologies and modern bioinformatics approaches allows us to apply them for characterization of AMP-derived genes and the identification of encoded immune-related peptides with the aid of genome and transcriptome mining. Here, we describe a universal bioinformatic approach based on the conserved BRICHOS domain as a search query for the identification of novel structurally unique AMP families in annelids. In this paper, we report the discovery of 13 novel BRICHOS-related peptides, ranging from 18 to 91 amino acid residues in length, in the cosmopolitan marine worm Heteromastus filiformis with the assistance of transcriptome mining. Two characteristic peptides with a low homology in relation to known AMPs-the α-helical amphiphilic linear peptide, consisting of 28 amino acid residues and designated as HfBRI-28, and the 25-mer ß-hairpin peptide, specified as HfBRI-25 and having a unique structure stabilized by two disulfide bonds-were obtained and analyzed as potential antimicrobials. Interestingly, both peptides showed the ability to kill bacteria via membrane damage, but mechanisms of their action and spectra of their activity differed significantly. Being non-cytotoxic towards mammalian cells and stable to proteolysis in the blood serum, HfBRI-25 was selected for further in vivo studies in a lethal murine model of the Escherichia coli infection, where the peptide contributed to the 100% survival rate in animals. A high activity against uropathogenic strains of E. coli (UPEC) as well as a strong ability to kill bacteria within biofilms allow us to consider the novel peptide HfBRI-25 as a promising candidate for the clinical therapy of urinary tract infections (UTI) associated with UPEC.

Molecular Insight into Ligand Binding and Transport by the Lentil Lipid Transfer Protein Lc-LTP2: The Role of Basic Amino Acid Residues at Opposite Entrances to the Hydrophobic Cavity.

Lipid transfer proteins (LTPs) realize their functions in plants due to their ability to bind and transport various ligands. Structures of many LTPs have been studied; however, the mechanism of ligand binding and transport is still not fully understood. In this work, we studied the role of Lys61 and Lys81 located near the "top" and "bottom" entrances to the hydrophobic cavity of the lentil lipid transfer protein Lc-LTP2, respectively, in these processes. Using site-directed mutagenesis, we showed that both amino acid residues played a key role in lipid binding to the protein. In experiments with calcein-loaded liposomes, we demonstrated that both the above-mentioned lysine residues participated in the protein interaction with model membranes. According to data obtained from fluorescent spectroscopy and TNS probe displacement, both amino acid residues are necessary for the ability of the protein to transfer lipids between membranes. Thus, we hypothesized that basic amino acid residues located at opposite entrances to the hydrophobic cavity of the lentil Lc-LTP2 played an important role in initial protein-ligand interaction in solution as well as in protein-membrane docking.

Marine Invertebrate Antimicrobial Peptides and Their Potential as Novel Peptide Antibiotics.

Marine invertebrates constantly interact with a wide range of microorganisms in their aquatic environment and possess an effective defense system that has enabled their existence for millions of years. Their lack of acquired immunity sets marine invertebrates apart from other marine animals. Invertebrates could rely on their innate immunity, providing the first line of defense, survival, and thriving. The innate immune system of marine invertebrates includes various biologically active compounds, and specifically, antimicrobial peptides. Nowadays, there is a revive of interest in these peptides due to the urgent need to discover novel drugs against antibiotic-resistant bacterial strains, a pressing global concern in modern healthcare. Modern technologies offer extensive possibilities for the development of innovative drugs based on these compounds, which can act against bacteria, fungi, protozoa, and viruses. This review focuses on structural peculiarities, biological functions, gene expression, biosynthesis, mechanisms of antimicrobial action, regulatory activities, and prospects for the therapeutic use of antimicrobial peptides derived from marine invertebrates.

Epithelial-Immune Cell Crosstalk Determines the Activation of Immune Cells In Vitro by the Human Cathelicidin LL-37 at Low Physiological Concentrations.

The only human cathelicidin, LL-37, is a host defense antimicrobial peptide with antimicrobial activities against protozoans, fungi, Gram(+) and Gram(-) bacteria, and enveloped viruses. It has been shown in experiments in vitro that LL-37 is able to induce the production of various inflammatory and anti-inflammatory cytokines and chemokines by different human cell types. However, it remains an open question whether such cytokine induction is physiologically relevant, as LL-37 exhibited its immunomodulatory properties at concentrations that are much higher (>20 µg/mL) than those observed in non-inflamed tissues (1-5 µg/mL). In the current study, we assessed the permeability of LL-37 across the Caco-2 polarized monolayer and showed that this peptide could pass through the Caco-2 monolayer with low efficiency, which predetermined its low absorption in the gut. We showed that LL-37 at low physiological concentrations (<5 µg/mL) was not able to directly activate monocytes. However, in the presence of polarized epithelial monolayers, LL-37 is able to activate monocytes through the MAPK/ERK signaling pathway and induce the production of cytokines, as assessed by a multiplex assay at the protein level. We have demonstrated that LL-37 is able to fulfill its immunomodulatory action in vivo in non-inflamed tissues at low physiological concentrations. In the present work, we revealed a key role of epithelial-immune cell crosstalk in the implementation of immunomodulatory functions of the human cathelicidin LL-37, which might shed light on its physiological action in vivo.

Design of Protegrin-1 Analogs with Improved Antibacterial Selectivity.

Protegrin-1 (PG-1) is a cationic ß-hairpin pore-forming antimicrobial peptide having a membranolytic mechanism of action. It possesses in vitro a potent antimicrobial activity against a panel of clinically relevant MDR ESKAPE pathogens. However, its extremely high hemolytic activity and cytotoxicity toward mammalian cells prevent the further development of the protegrin-based antibiotic for systemic administration. In this study, we rationally modulated the PG-1 charge and hydrophobicity by substituting selected residues in the central ß-sheet region of PG-1 to design its analogs, which retain a high antimicrobial activity but have a reduced toxicity toward mammalian cells. In this work, eight PG-1 analogs with single amino acid substitutions and five analogs with double substitutions were obtained. These analogs were produced as thioredoxin fusions in Escherichia coli. It was shown that a significant reduction in hemolytic activity without any loss of antimicrobial activity could be achieved by a single amino acid substitution, V16R in the C-terminal ß-strand, which is responsible for the PG-1 oligomerization. As the result, a selective analog with a ≥30-fold improved therapeutic index was obtained. FTIR spectroscopy analysis of analog, [V16R], revealed that the peptide is unable to form oligomeric structures in a membrane-mimicking environment, in contrast to wild-type PG-1. Analog [V16R] showed a reasonable efficacy in septicemia infection mice model as a systemic antibiotic and could be considered as a promising lead for further drug design.

Immunomodulatory Effects of the Pea Defensin Psd1 in the Caco-2/Immune Cells Co-Culture upon Candida albicans Infection.

Candidiasis is one of the most common fungal diseases that can pose a threat to life in immunodeficient individuals, particularly in its disseminated form. Not only fungal invasion but also fatal infection-related inflammation are common causes of systemic candidiasis. In this study, we investigated in vitro immunomodulatory properties of the antifungal pea defensin Psd1 upon Candida albicans infection. Using the real-time PCR, we showed that Psd1 inhibited the antimicrobial peptide HBD-2 and pro-inflammatory cytokines IL-1 and IL-8 downregulation at mRNA level in epithelium cells caused by C. albicans infection. By using the Caco-2/immune cells co-culture upon C. albicans infection and the multiplex xMAP assay, we demonstrated that this pathogenic fungus induced a pronounced host defense response; however, the cytokine responses were different in the presence of dendritic cells or monocytes. We revealed that Psd1 at a low concentration (2 µM) had a pronounced immunomodulatory effect on the Caco-2/immune cells co-culture upon fungal infection. Thus, we hypothesized that the pea defensin Psd1 might be an effective agent in the treatment of candidiasis not only due to its antifungal activity, but also owing to its ability to modulate a protective immune response upon infection.

Genomic Insights into Bacterial Resistance to Proline-Rich Antimicrobial Peptide Bac7.

Proline-rich antimicrobial peptides (PrAMPs) having a potent antimicrobial activity and a modest toxicity toward mammalian cells attract much attention as new templates for the development of antibiotic drugs. However, a comprehensive understanding of mechanisms of bacterial resistance development to PrAMPs is necessary before their clinical application. In this study, development of the resistance to the proline-rich bovine cathelicidin Bac71-22 derivative was characterized in the multidrug-resistant Escherichia coli clinical isolate causing the urinary tract infection. Three Bac71-22-resistant strains with ≥16-fold increase in minimal inhibitory concentrations (MICs) were selected by serially passaging after four-week experimental evolution. It was shown that in salt-containing medium, the resistance was mediated by inactivation of the SbmA transporter. The absence of salt in the selection media affected both dynamics and main molecular targets under selective pressure: a point mutation leading to the amino acid substitution N159H in the WaaP kinase responsible for heptose I phosphorylation in the LPS structure was also found. This mutation led to a phenotype with a decreased susceptibility to both the Bac71-22 and polymyxin B. Screening of antimicrobial activities with the use of a wide panel of known AMPs, including the human cathelicidin LL-37 and conventional antibiotics, against selected strains indicated no significant cross-resistance effects.

Specific Binding of the α-Component of the Lantibiotic Lichenicidin to the Peptidoglycan Precursor Lipid II Predetermines Its Antimicrobial Activity.

To date, a number of lantibiotics have been shown to use lipid II-a highly conserved peptidoglycan precursor in the cytoplasmic membrane of bacteria-as their molecular target. The α-component (Lchα) of the two-component lantibiotic lichenicidin, previously isolated from the Bacillus licheniformis VK21 strain, seems to contain two putative lipid II binding sites in its N-terminal and C-terminal domains. Using NMR spectroscopy in DPC micelles, we obtained convincing evidence that the C-terminal mersacidin-like site is involved in the interaction with lipid II. These data were confirmed by the MD simulations. The contact area of lipid II includes pyrophosphate and disaccharide residues along with the first isoprene units of bactoprenol. MD also showed the potential for the formation of a stable N-terminal nisin-like complex; however, the conditions necessary for its implementation in vitro remain unknown. Overall, our results clarify the picture of two component lantibiotics mechanism of antimicrobial action.

Bet v 1-independent sensitization to major allergens in Fagales pollen: Evidence at the T-cell level.

BACKGROUND: In birch-dominated areas, allergies to pollen from trees of the order Fagales are considered to be initiated by the major birch pollen allergen Bet v 1. However, the sensitizing activity of Bet v 1-homologs in Fagales pollen might be underestimated. Allergen-specific T-cells are crucial in the sensitization process. The T-cell response to major allergens from alder, hazel, oak, hornbeam, chestnut, beech, and chestnut pollen has not yet been analyzed. Here, we characterized the cellular cross-reactivity of major allergens in Fagales pollen with Bet v 1. METHODS: T-cell-lines (TCL) were established from allergic individuals with Aln g 1, Car b 1, Ost c 1, Cor a 1, Fag s 1, Cas s 1, and Que a 1, and tested for reactivity with Bet v 1 and synthetic overlapping 12-mer peptides representing its primary sequence. Aln g 1-specific TCL was additionally tested with Aln g 1-derived peptides and all allergens. IgE-competition experiments with Aln g 1 and Bet v 1 were performed. RESULTS: T-cell-lines initiated with Fagales pollen allergens varied strongly in their reactivity with Bet v 1 and by the majority responded stronger to the original stimulus. Cross-reactivity was mostly restricted to the epitope Bet v 1142-153 . No distinct cross-reactivity of Aln g 1-specific T-cells with Bet v 1 was detected. Among 22 T-cell epitopes, Aln g 1 contained two immunodominant epitopes. Bet v 1 inhibited IgE-binding to Aln g 1 less potently than Aln g 1 itself. CONCLUSION: The cellular cross-reactivity of major Fagales pollen allergens with Bet v 1 was unincisive, particularly for Aln g 1, most akin to Bet v 1. Our results indicate that humoral and cellular responses to these allergens are not predominantly based on cross-reactivity with the major birch pollen allergen but suggest a Bet v 1-independent sensitization in individuals from birch tree-dominated areas.

Antimicrobial Activity and Immunomodulatory Properties of Acidocin A, the Pediocin-like Bacteriocin with the Non-Canonical Structure.

Pediocin-like bacteriocins are among the natural antimicrobial agents attracting attention as scaffolds for the development of a new generation of antibiotics. Acidocin A has significant structural differences from most other members of this subclass. We studied its antibacterial and cytotoxic activity, as well as effects on the permeability of E. coli membranes in comparison with avicin A, the typical pediocin-like bacteriocin. Acidocin A had a more marked tendency to form an alpha-helical structure upon contact with detergent micelles, as was shown by CD spectroscopy, and demonstrated considerably less specific mode of action: it inhibited growth of Gram-positive and Gram-negative strains, which were unsusceptible to avicin A, and disrupted the integrity of outer and inner membranes of E. coli. However, the peptide retained a low toxicity towards normal and tumor human cells. The effect of mutations in the pediocin box of acidocin A (on average, a 2-4-fold decrease in activity) was less pronounced than is usually observed for such peptides. Using multiplex analysis, we showed that acidocin A and avicin A modulated the expression level of a number of cytokines and growth factors in primary human monocytes. Acidocin A induced the production of a number of inflammatory mediators (IL-6, TNFα, MIG/CXCL9, MCP-1/CCL2, MCP-3/CCL7, and MIP-1ß) and inhibited the production of some anti-inflammatory factors (IL-1RA, MDC/CCL22). We assumed that the activity of acidocin A and similar peptides produced by lactic acid bacteria might affect the functional state of the human intestinal tract, not only through direct inhibition of various groups of symbiotic and pathogenic bacteria, but also via immunomodulatory effects.

Structural Features, Mechanisms of Action, and Prospects for Practical Application of Class II Bacteriocins.

Bacteriocins are antimicrobial peptides ribosomally synthesized by both Gram-negative and Gram-positive bacteria, as well as by archaea. Bacteriocins are usually active against phylogenetically related bacteria, providing competitive advantage to their producers in the natural bacterial environment. However, some bacteriocins are known to have a broader spectrum of antibacterial activity, including activity against multidrug-resistant bacterial strains. Multitude of bacteriocins studied to date are characterized by a wide variety of chemical structures and mechanisms of action. Existing classification systems for bacteriocins take into account structural features and biosynthetic pathways of bacteriocins, as well as the phylogenetic affiliation of their producing organisms. Heat-stable bacteriocins with molecular weight of less than 10 kDa from Gram-positive and Gram-negative producers are divided into post-translationally modified (class I) and unmodified peptides (class II). In recent years there has been an increasing interest in the class II bacteriocins as potential therapeutic agents that can help to combat antibiotic-resistant infections. Advantages of unmodified peptides are relative simplicity of their biotechnological production in heterologous systems and chemical synthesis. Potential for the combined use of bacteriocins with other antimicrobial agents allowing to enhance their efficacy, low probability of cross-resistance development, and ability of probiotic strains to produce bacteriocins in situ make them promising candidate compounds for creation of new drugs. The review focuses on structural diversity of the class II bacteriocins and their practical relevance.

Structural and Immunologic Properties of the Major Soybean Allergen Gly m 4 Causing Anaphylaxis.

Gly m 4 is the major soybean allergen, causing birch pollen cross allergic reactions. In some cases, Gly m 4-mediated anaphylaxis takes place, but the causative factors are still unknown. Here, we studied the structural and immunologic properties of Gly m 4 to shed light on this phenomenon. We showed that Gly m 4 retained its structure and IgE-binding capacity after heating. Gly m 4 was cleaved slowly under nonoptimal gastric conditions mimicking duodenal digestion, and IgE from the sera of allergic patients interacted with the intact allergen rather than with its proteolytic fragments. Similar peptide clusters of Bet v 1 and Gly m 4 were formed during allergen endolysosomal degradation in vitro, but their sequence identity was insignificant. Animal polyclonal anti-Gly m 4 and anti-Bet v 1 IgG weakly cross-reacted with Bet v 1 and Gly m 4, respectively. Thus, we supposed that not only conserved epitopes elicited cross-reactivity with Bet v 1, but also variable epitopes were present in the Gly m 4 structure. Our data suggests that consumption of moderately processed soybean-based drinks may lead to the neutralizing of gastric pH as a result of which intact Gly m 4 can reach the human intestine and cause IgE-mediated system allergic reactions.

In Vitro Modulation of Complement Activation by Therapeutically Prospective Analogues of the Marine Polychaeta Arenicin Peptides.

The widespread resistance to antibiotics in pathogenic bacteria makes the development of a new generation of antimicrobials an urgent task. The development of new antibiotics must be accompanied by a comprehensive study of all of their biological activities in order to avoid adverse side-effects from their application. Some promising antibiotic prototypes derived from the structures of arenicins, antimicrobial peptides from the lugworm Arenicola marina, have been developed. Previously, we described the ability of natural arenicins -1 and -2 to modulate the human complement system activation in vitro. In this regard, it seems important to evaluate the effect of therapeutically promising arenicin analogues on complement activation. Here, we describe the complement-modulating activity of three such analogues, Ar-1[V8R], ALP1, and AA139. We found that the mode of action of Ar-1[V8R] and ALP1 on the complement was similar to that of natural arenicins, which can both activate and inhibit the complement, depending on the concentration. However, Ar-1[V8R] behaved predominantly as an inhibitor, showing only a moderate increase in C3a production in the alternative pathway model and no enhancement at all of the classical pathway of complement activation. In contrast, the action of ALP1 was characterized by a marked increase in the complement activation through the classical pathway in the concentration range of 2.5-20 µg/mL. At the same time, at higher concentrations (80-160 µg/mL), this peptide exhibited a complement inhibitory effect characteristic of the other arenicins. Peptide AA139, like other arenicins, exhibited an inhibitory effect on complement at a concentration of 160 µg/mL, but was much less pronounced. Overall, our results suggest that the effect on the complement system should be taken into account in the development of antibiotics based on arenicins.

Innate Immunity Mechanisms in Marine Multicellular Organisms.

The innate immune system provides an adequate response to stress factors and pathogens through pattern recognition receptors (PRRs), located on the surface of cell membranes and in the cytoplasm. Generally, the structures of PRRs are formed by several domains that are evolutionarily conserved, with a fairly high degree of homology in representatives of different species. The orthologs of TLRs, NLRs, RLRs and CLRs are widely represented, not only in marine chordates, but also in invertebrates. Study of the interactions of the most ancient marine multicellular organisms with microorganisms gives us an idea of the evolution of molecular mechanisms of protection against pathogens and reveals new functions of already known proteins in ensuring the body's homeostasis. The review discusses innate immunity mechanisms of protection of marine invertebrate organisms against infections, using the examples of ancient multicellular hydroids, tunicates, echinoderms, and marine worms in the context of searching for analogies with vertebrate innate immunity. Due to the fact that mucous membranes first arose in marine invertebrates that have existed for several hundred million years, study of their innate immune system is both of fundamental importance in terms of understanding molecular mechanisms of host defense, and of practical application, including the search of new antimicrobial agents for subsequent use in medicine, veterinary and biotechnology.

Antifungal Activity, Structural Stability, and Immunomodulatory Effects on Human Immune Cells of Defensin from the Lentil Lens culinaris.

An increase in the frequency of mycoses and spreading of multidrug-resistant fungal pathogens necessitates the search for new antifungal agents. Earlier, we isolated the novel defensin from lentil Lensculinaris seeds, designated as Lc-def, which inhibited the growth of phytopathogenic fungi. Here, we studied an antifungal activity of Lc-def against human pathogenic Candida species, structural stability of the defensin, and its immunomodulatory effects that may help to prevent fungal infection. We showed that Lc-def caused 50% growth inhibition of clinical isolates of Candida albicans, C. krusei, and C. glabrata at concentrations of 25-50 µM, but was not toxic to different human cells. The lentil defensin was resistant to proteolysis by C. albicans and was not cleaved during simulated gastroduodenal digestion. By using the multiplex xMAP assay, we showed for the first time for plant defensins that Lc-def increased the production of such essential for immunity to candidiasis pro-inflammatory cytokines as IL-12 and IL-17 at the concentration of 2 µM. Thus, we hypothesized that the lentil Lc-def and plant defensins in general may be effective in suppressing of mucocutaneous candidiasis due to their antifungal activity, high structural stability, and ability to activate a protective immune response.

Novel ß-Hairpin Peptide from Marine Polychaeta with a High Efficacy against Gram-Negative Pathogens.

In recent years, new antibiotics targeting multidrug resistant Gram-negative bacteria have become urgently needed. Therefore, antimicrobial peptides are considered to be a novel perspective class of antibacterial agents. In this study, a panel of novel BRICHOS-related ß-hairpin antimicrobial peptides were identified in transcriptomes of marine polychaeta species. Two of them-abarenicin from Abarenicola pacifica and UuBRI-21 from Urechis unicinctus-possess strong antibacterial potential in vitro against a wide panel of Gram-negative bacteria including drug-resistant strains. Mechanism of action assays demonstrate that peptides disrupt bacterial and mammalian membrane integrity. Considering the stronger antibacterial potential and a low ability of abarenicin to be bound by components of serum, this peptide was selected for further modification. We conducted an alanine and arginine scanning of abarenicin by replacing individual amino acids and modulating hydrophobicity so as to improve its antibacterial potency and membrane selectivity. This design approach allowed us to obtain the Ap9 analog displaying a high efficacy in vivo in the mice septicemia and neutropenic mice peritonitis models. We demonstrated that abarenicin analogs did not significantly induce bacterial resistance after a four-week selection experiment and acted on different steps of the biofilm formation: (a) killing bacteria at their planktonic stage and preventing biofilm formation and (b) degrading pre-formed biofilm and killing embedded bacteria. The potent antibacterial and antibiofilm activity of the abarenicin analog Ap9 with its high efficacy in vivo against Gram-negative infection in mice models makes this peptide an attractive candidate for further preclinical investigation.

How Do Pollen Allergens Sensitize?

Plant pollen is one of the main sources of allergens causing allergic diseases such as allergic rhinitis and asthma. Several allergens in plant pollen are panallergens which are also present in other allergen sources. As a result, sensitized individuals may also experience food allergies. The mechanism of sensitization and development of allergic inflammation is a consequence of the interaction of allergens with a large number of molecular factors that often are acting in a complex with other compounds, for example low-molecular-mass ligands, which contribute to the induction a type 2-driven response of immune system. In this review, special attention is paid not only to properties of allergens but also to an important role of their interaction with lipids and other hydrophobic molecules in pollen sensitization. The reactions of epithelial cells lining the nasal and bronchial mucosa and of other immunocompetent cells will also be considered, in particular the mechanisms of the activation of B and T lymphocytes and the formation of allergen-specific antibody responses.