Bitop (Germany)

Nonpharmacological therapies with a good tolerability and safety profile are of interest to many patients with allergic rhinitis, as a relevant proportion of them have reservations about guideline-concordant pharmacological therapies due to their local irritations and side effects. Ectoine is a bacterial-derived extremolyte with an ability to protect proteins and biological membranes against damage caused by extreme conditions of salinity, drought, irradiation, pH, and temperature. Evidence from preclinical and clinical studies attests its effectiveness in the treatment of several inflammatory diseases, including allergic rhinitis. In this review, we analyzed 14 recent clinical trials investigating ectoine nasal spray in patients with allergic rhinitis and/or conjunctivitis, including sensitive patient groups like children or pregnant women. Some studies investigated monotherapy with ectoine; others investigated combination therapy of ectoine and an antihistamine or a corticosteroid. Analysis of the study results demonstrated that patients with mild-to-moderate symptoms of allergic rhinitis can be successfully treated with ectoine-containing nasal spray. When applied as monotherapy, ectoine exerted noninferior effects compared to first-line therapies such as antihistamines and cromoglicic acid. Using ectoine as an add-on therapy to antihistamines or intranasal glucocorticosteroids accelerated symptom relief by days and improved the level of symptom relief. Importantly, concomitant treatment with ectoine was proven beneficial in a group of difficult-to-treat patients suffering from moderate-to-severe rhinitis symptoms. Taken together, the natural substance ectoine represents a viable alternative for allergic rhinitis and conjunctivitis patients who wish to avoid local reactions and side effects associated with pharmacological therapies.

Understanding adaptation to extreme environments remains a challenge of high biotechnological potential for fundamental molecular biology. The cytosol of many microorganisms, isolated from saline environments, reversibly accumulates molar concentrations of the osmolyte ectoine to counterbalance fluctuating external salt concentrations. Although they have been studied extensively by thermodynamic and spectroscopic methods, direct experimental structural data have, so far, been lacking on ectoine-water-protein interactions. In this paper, in vivo deuterium labeling, small angle neutron scattering, neutron membrane diffraction and inelastic scattering are combined with neutron liquids diffraction to characterize the extreme ectoine-containing solvent and its effects on purple membrane of H. salinarum and E. coli maltose binding protein. The data reveal that ectoine is excluded from the hydration layer at the membrane surface and does not affect membrane molecular dynamics, and prove a previous hypothesis that ectoine is excluded from a monolayer of dense hydration water around the soluble protein. Neutron liquids diffraction to atomic resolution shows how ectoine enhances the remarkable properties of H-bonds in water—properties that are essential for the proper organization, stabilization and dynamics of biological structures.

Ectoin ist eine zyklische Aminosäure die Geweben Schutz vor Noxen wie Temperatur oder Salz bietet. Positive Eigenschaften Ectoin-haltiger Formulierungen konnten schon bei der allergischen Rhinitis und Konjunktivitis, der Neurodermitis und zum Schutz vor trockenen Hautzuständen gezwigt werden. Die vorliegende Studie zeigt, dass die Ectoin-Inhalationslösung die aufgrund chronisch entzündeter Atemwege bestehende bronchiale Hyperreagibilität bei Asthmatikern verbessert.

The halophilic γ-proteobacterium Halomonas elongata DSM 2581T thrives at high salinity by synthesizing and accumulating the compatible solute ectoine. Ectoine levels are highly regulated according to external salt levels but the overall picture of its metabolism and control is not well understood. Apart from its critical role in cell adaptation to halophilic environments, ectoine can be used as a stabilizer for enzymes and as a cell protectant in skin and health care applications and is thus produced annually on a scale of tons in an industrial process using H. elongata as producer strain. This paper presents the complete genome sequence of H. elongata (4 061 296 bp) and includes experiments and analysis identifying and characterizing the entire ectoine metabolism, including a newly discovered pathway for ectoine degradation and its cyclic connection to ectoine synthesis. The degradation of ectoine (doe) proceeds via hydrolysis of ectoine (DoeA) to Nα-acetyl-l-2,4-diaminobutyric acid, followed by deacetylation to diaminobutyric acid (DoeB). In H. elongata, diaminobutyric acid can either flow off to aspartate or re-enter the ectoine synthesis pathway, forming a cycle of ectoine synthesis and degradation. Genome comparison revealed that the ectoine degradation pathway exists predominantly in non-halophilic bacteria unable to synthesize ectoine. Based on the resulting genetic and biochemical data, a metabolic flux model of ectoine metabolism was derived that can be used to understand the way H. elongata survives under varying salt stresses and that provides a basis for a model-driven improvement of industrial ectoine production.

Abstract High-risk human papillomaviruses (HPV) such as HPV16 are associated with the development of cervical cancer. The HPV16-E6 and HPV16-E7 oncoproteins are expressed throughout the replicative cycle of the virus and are necessary for the onset and maintenance of malignant transformation. Both these tumor-specific antigens are considered as potential targets for specific CTL-mediated immunotherapy. The adenylate cyclase (CyaA) of Bordetella pertussis is able to target dendritic cells through specific interaction with the αMβ2 integrin. It has been previously shown that this bacterial protein could be used to deliver CD4+ and CD8+ T cell epitopes to the MHC class II and class I presentation pathways to trigger specific Th and CTL responses in vivo, providing protection against subsequent viral or tumoral challenge. Here, we constructed recombinant CyaA containing either the full sequence or various subfragments from the HPV16-E7 protein. We show that, when injected to C57BL/6 mice in absence of any adjuvant, these HPV16-recombinant CyaAs are able to induce specific Th1 and CTL responses. Furthermore, when injected into mice grafted with HPV16-E7-expressing tumor cells (TC-1), one of these recombinant proteins was able to trigger complete tumor regression in 100% of the animals tested. This therapeutic efficacy compared favorably to that of strongly adjuvanted peptide and was marginally affected by prior immunity to CyaA protein. This study represents the first in vivo demonstration of the antitumoral therapeutic activity of recombinant CyaA proteins carrying human tumor–associated antigens and paves the way for the testing of this vector in clinical trials.