Untersuchungen zum Wechselspiel von multi-resistenten Pseudomonas aeruginosa, kommensaler Darmmikrobiota und Immunantworten bei muriner Darmentzündung

Die weltweite Zunahme von nosokomialen Infektionen mit multiresistenten (multidrug resistant; MDR) Gram-negativen Bakterien wie Pseudomonas (P.) aeruginosa ist eine Bedrohung vor allem für immunsupprimierte, hospitalisierte und chronisch pulmonal erkrankte Patienten. Obwohl der Gastrointestinaltrakt (GIT) eine mögliche Infektionsquelle darstellt, ist wenig darüber bekannt unter welchen Bedingungen es zu einer Kolonisierung des Darms mit MDR P. aeruginosa kommt, wie sich diese auf die intestinale, extra-intestinale und systemische Immunantwort des Wirtes auswirkt und welche Rolle eine Darmentzündung dabei spielt. In der vorliegenden Arbeit führten wir Kolonisationsversuche an konventionell kolonisierten sowie sekundär abiotischen Mäusen durch, die zeigten, dass durch die Eliminierung der konventionellen Darmmikrobiota mittels oraler Breitspektrumantibiose, die natürliche Kolonisationsresistenz gegenüber P. aeruginosa aufgehoben wird. Die Rekonstitution sekundär abiotischer Mäuse mit humaner oder muriner Darmmikrobiota mittels fäkaler Mikrobiota-Transplantation (FMT) führte nur zu einem partiellen Schutz vor Kolonisierung. Die orale Gabe von P. aeruginosa führte sowohl in sekundär abiotischen als auch in mit humaner oder muriner Darmmikrobiota rekonstituierten Mäusen zu intestinalen Immunantworten, die sich in einem Einstrom von Immunzellen wie Makrophagen und Monozyten in die Darmmukosa sowie erhöhten Konzentrationen pro-inflammatorischer Zytokine, wie dem Tumornekrosefaktor (TNF) äußerten. Die gesteigerte Zytokinausschüttung war jedoch nicht nur begrenzt auf den GIT, sondern konnte auch auf systemischer Ebene in der Milz beobachtet werden. Weiterhin konnten wir in Mäusen mit akuter Toxoplasma (T.) gondii induzierter Ileitis sowie IL-10 Knockout (IL-10-/-) Mäusen mit chronischer Kolitis zeigen, dass eine Darmentzündung Mäuse empfänglich für eine P. aeruginosa Kolonisierung macht. Während wir im akuten Inflammationsmodell keine Verschlimmerung der Darmentzündung nach T. gondii Infektion nachweisen konnten, führte die mehrwöchige Darmkolonisierung mit P. aeruginosa im chronischen Inflammationsmodell zu einer Exazerbation der chronischen Kolitis, die sich durch einen gesteigerten Einstrom intestinaler Immunzellen und erhöhte Konzentrationen pro-inflammatorischer Zytokine wie TNF und Interferon-γ (IFN-γ) in den mesenterischen Lymphknoten (MLN) und im Serum äußerte. Zusammenfassend konnten wir zeigen, dass die Darmmikrobiota maßgeblich zur Kolonisationsresistenz gegenüber P. aeruginosa beiträgt und dass deren Störung zu einer intestinalen Kolonisierung mit dem opportunistischen Pathogen führen kann. Weiterhin wurde deutlich, dass eine reine intestinale Kolonisierung mit P. aeruginosa zu einer pro-inflammatorischen Immunantwort im Wirtsorganismus führt. Darüber hinaus fördert eine Darmentzündung die Kolonisierung mit P. aeruginosa, welche wiederum zu einer Verschlechterung des zugrundeliegenden Krankheitsbildes führt.The worldwide growing incidence of nosocomial infections with multidrug resistant (MDR) Gram-negative bacteria such as Pseudomonas (P.) aeruginosa is a threat especially to immunocompromised or hospitalized patients and patients suffering from chronic pulmonary diseases. Although the gastrointestinal tract (GIT) is a potential source for infections, only little is known about conditions leading to intestinal colonization with MDR P. aeruginosa, how the latter affects the intestinal, extra-intestinal and systemic immune response of the host and the impact intestinal inflammation has hereon. In the present work colonization experiments in conventionally colonized as well as secondary abiotic mice revealed that elimination of the conventional microbiota through oral treatment with broad-spectrum antibiotics abrogates the natural colonization resistance directed against P. aeruginosa. Reconstitution of secondary abiotic mice with either human or murine microbiota through fecal microbiota-transplantation (FMT) only partially protected from colonization. Intestinal carriage of P. aeruginosa led to intestinal immune responses not only in secondary abiotic mice but also in mice reconstituted with human or murine microbiota, as indicated by increased numbers of intestinal immune cells such as macrophages and monocytes as well as elevated concentrations of pro-inflammatory cytokines such as tumor necrosis factor (TNF). Pro-inflammatory cytokine responses were not limited to the GIT, but could also be observed systemically (i. e. in the spleen). Furthermore, experiments in mice with acute Toxoplasma (T.) gondii induced ileitis and IL-10 Knockout (IL-10-/-) mice with chronic colitis revealed that intestinal inflammation renders mice more susceptible for P. aeruginosa carriage. No aggravation of the pronounced immune response could be observed in mice with acute T. gondii induced ileitis. Conversely, the intestinal colonization with P. aeruginosa in the chronic inflammation model resulted in a distinct exacerbation of chronic colitis, as indicated by an increased influx of intestinal immune cells and elevated concentrations of pro-inflammatory cytokines such as TNF and interferon-γ (IFN-γ) in the mesenteric lymph nodes (MLN) and serum. Taken together, our studies underline the important impact of the intestinal microbiota on the colonization resistance against P. aeruginosa and that the perturbation of the complex intestinal ecosystem may lead to intestinal colonization with the opportunistic pathogen. Furthermore, it became clear that mere intestinal carriage of P. aeruginosa results in pro-inflammatory immune responses of the host. Moreover, intestinal inflammation renders mice more susceptible to intestinal P. aeruginosa colonization which deteriorates chronic colitis

Spontaneous emergence of angular momentum Josephson oscillations in coupled annular Bose-Einstein condensates

We investigate the nonlinear dynamics of two coupled annular Bose-Einstein condensates (BECs). For certain values of the coupling strength the nonrotating ground state is unstable with respect to fluctuations in the higher angular momentum modes. The two branched Bogoliubov spectrum exhibits distinct regions of instability enabling one to selectively occupy certain angular momentum modes. For sufficiently long evolution times angular momentum Josephson oscillations spontaneously appear, breaking the initial chiral symmetry of the BECs

Time-Averaged Adiabatic Potentials: Versatile traps and waveguides for ultracold quantum gases

We demonstrate a novel class of trapping potentials, time-averaged adiabatic potentials (TAAP) which allows the generation of a large variety of traps and waveguides for ultracold atoms. Multiple traps can be coupled through controllable tunneling barriers or merged altogether. We present analytical expressions for pancake-, cigar-, and ring- shaped traps. The ring-geometry is of particular interest for guided matter-wave interferometry as it provides a perfectly smooth waveguide of controllable diameter, and thus a tunable sensitivity of the interferometer.Comment: 5 pages, 3 figure

Composite Fermions with Spin Freedom

General rule for the composite fermion transformation, when the spins of the electrons are not polarized is derived. Condition for the quantum phase transition between various spin states is obtained based on the rule. This rule gives foundation for the experimental determination of the mass and $g$-factor of the composite fermion.Comment: 5 pages with 1 ps figure, Revtex, to be published in J. Phys. Soc. Jpn. Vol.68 No.10. Misprints are correcte

Correlation between specific ion adsorption at the air/water interface and long-range interactions in colloidal systems

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Specific ion effects are of high impact in colloid science and dominate processes in aqueous systems from protein folding or precipitation to ordering of particles or macromolecules in bulk solutions. Due to the large internal interface of colloidal systems especially interfacial ion effects are of importance. This paper presents a new insight into the specific ion effects at the air/water interface of monovalent electrolyte solutions and their consequences for long-range interactions in colloidal systems. Solely, in an asymmetric film (i.e. wetting film) one can determine the sign and precise value of the surface potential of the free air/water surface. It is shown that the all over charges of the interfacial region, which are affected by the type of ion, dominate the interfacial forces even over several tens of nm. This is of interest for tailoring the stability of colloidal systems. It is clearly shown that the air/water interface is negatively charged and that both anions and cations affect the surface potential even at very low electrolyte concentrations (10−4 M).DFG, SPP 1273, Kolloidverfahrenstechni

Interferometric determination of the s- and d-wave scattering amplitudes in 87^{87}Rb

We demonstrate an interference method to determine the low-energy elastic scattering amplitudes of a quantum gas. We linearly accelerate two ultracold atomic clouds up to energies of 1.2 mK and observe the collision halo by direct imaging in free space. From the interference between $s$- and $d$- partial waves in the differential scattering pattern we extract the corresponding phase shifts. The method does not require knowledge of the atomic density. This allows us to infer accurate values for the $s$- and d-wave scattering amplitudes from the zero-energy limit up to the first Ramsauer minimum using only the Van der Waals $C_{6}$ coefficient as theoretical input. For the $^{87}$Rb triplet potential, the method reproduces the scattering length with an accuracy of 6%.Comment: 4 pages, 3 figure