Antimikrobielle peptide dissertation

Antimikrobielle peptide dissertation

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Since inception, we have amassed top talent through rigorous recruiting process in addition to using sophisticated design and tools in order Antimikrobielle peptide dissertation Peptide Dissertation to deliver the. Staphylococcus aureus is an important zoonotic pathogen, which can cause various diseases in humans and animals.

The treatment of S. Methicillin-resistant S. aureus MRSA isolates, including the livestock-associated MRSA LA-MRSArepresent a particular problem, since they are often resistant to multiple classes of antimicrobial agents.

Therefore, alternatives to antibiosis, like the boosting of the immune system, are urgently needed. Since former studies already demonstrated the importance of antimicrobial peptides AMPs antimikrobielle peptide dissertation, especially cathelicidins, in the antimikrobielle peptide dissertation response against S. aureus infections, AMPs might be promising candidates for the treatment of staphylococcal infections, antimikrobielle peptide dissertation, antimikrobielle peptide dissertation.

Hence, the aim of this thesis was to investigate mechanisms, which antimikrobielle peptide dissertation have an influence on the interaction of cathelicidins with S. aureus, particularly LA-MRSA. For this purpose, antimikrobielle peptide dissertationthe minimal inhibitory concentrations MICs antimikrobielle peptide dissertation five cathelicidins of human, mouse, rabbit or cattle origin were determined for a collection of LA-MRSA isolates Chapter 4.

All isolates, regardless of their origin, showed similar cathelicidin-specific MICs, antimikrobielle peptide dissertation, antimikrobielle peptide dissertation. Furthermore, the influence of known antibiotic and heavy metal-resistance genes on the MICs of the AMPs was analyzed. The presence of resistance genes did not alter the MICs, indicating that the tested antibiotic or heavy antimikrobielle peptide dissertation genes do not confer resistance against the tested AMPs.

Furthermore, MICs of the different AMPs were determined in the presence and absence of different efflux pump inhibitors Chapter 5. In the presence of one inhibitor, 1- 1-naphthylmethyl -piperazine NMPwhich inhibits RND efflux pumps, the MICs for CAP18, antimikrobielle peptide dissertation, a rabbit cathelicidin, decreased significantly, antimikrobielle peptide dissertation.

Moreover, S. aureus mutants, whose RND efflux pump SecDF was functionally deleted or lacking, showed in comparison to their initial SecDF-positive strain and a complemented mutant also significantly lower MICs for CAP18 and the bovine BMAP For the remaining cathelicidins this phenotype was not seen. Since cathelicidins play a key role in the defense of neutrophils against bacterial infections, the last part of the thesis dealt with the question, whether the efflux pump SecDF, in addition to the alteration of the in vitro determined MICs, has also an impact on the susceptibility of S.

aureus to the antimicrobial functions of neutrophils Chapter 6. Thus, human and bovine whole blood as well as bovine neutrophils were incubated with a SecDF-positive wildtype WT strain, a SecDF-deficient mutant strain as well as a SecDF-complemented strain and their survival was measured. The strain without SecDF showed a better survival in the presence of human blood and bovine neutrophils. The reasons for this observation remain to be investigated.

These data indicate that SecDF is able to influence the antimikrobielle peptide dissertation of S. aureus in human blood and in the presence of bovine neutrophils. Taken together, these results show species-specific differences in the interaction of cathelicidins with S.

aureus, particularly with a focus on the activity of the bacterial antimikrobielle peptide dissertation pump SecDF. Since the tested resistance genes have no impact on the MICs for the different AMPs, the use of AMPs against multi-resistant S. aureus isolates might be a promising alternative to antibiotics. Staphylococcus aureus ist ein wichtiger zoonotischer Krankheitserreger, welcher bei Menschen und Tieren eine Antimikrobielle peptide dissertation von Erkrankungen verursachen kann.

Durch die zunehmende Resistenz von S. aureus gegenüber antimikrobiellen Wirkstoffen wird die Bekämpfung von Infektionen, antimikrobielle peptide dissertation, an denen dieser Erreger ursächlich beteiligt ist, erheblich erschwert.

Ein besonderes Problem stellen dabei Methicillin-resistente Antimikrobielle peptide dissertation. Künftig werden dringend Behandlungsalternativen zur Antibiose benötigt, wie zum Bespiel die Stärkung des Immunsystems. Da bereits frühere Antimikrobielle peptide dissertation gezeigt haben, wie wichtig antimikrobielle Peptide AMPs und hierbei besonders Cathelicidine für die Immunantwort gegenüber S.

aureus-Infektionen sind, stellen AMPs vielversprechende Kandidaten für die Behandlung von Staphylokokkeninfektionen dar. Daher war das Ziel dieser These, antimikrobielle peptide dissertationAntimikrobielle peptide dissertation zu untersuchen, welche einen möglichen Einfluss auf die Interaktion antimikrobielle peptide dissertation Cathelicidinen mit S.

aureus, insbesondere LA-MRSA, antimikrobielle peptide dissertation, haben. Zu diesem Zweck wurden LA-MRSA-Isolate hinsichtlich ihrer minimalen Hemmkonzentrationen MHKs für fünf Cathelicidine, welche von der Maus, antimikrobielle peptide dissertation Menschen, dem Kaninchen und dem Rind stammen, untersucht Kapitel 4. Unabhängig von ihrer Herkunft zeigten alle Isolate Cathelicidin-spezifisch annähernd gleiche MHK-Werte.

Des Weiteren antimikrobielle peptide dissertation der Einfluss von bekannten Antibiotika- und Schwermetall-Resistenzgenen auf die AMP-MHK Werte analysiert.

Die Präsenz von Resistenzgenen veränderte die AMP-MHKs nicht, woraus sich schlussfolgern lässt, dass die antimikrobielle peptide dissertation antimikrobiellen Resistenzgene oder Schwermetall-Resistenzgene keine Resistenz gegenüber den getesteten AMPs vermitteln. Ferner wurden AMP-MHKs in An- und Abwesenheit unterschiedlicher Efflux Pumpen-Inhibitoren ermittelt Kapitel 5. In der Anwesenheit eines Inhibitors, 1- 1-Naphthylmethyl -Piperazine NMPder RND Efflux Pumpen inhibiert, sanken die MHKs für CAP18, ein Cathelicidin vom Kaninchen, signifikant.

Des Antimikrobielle peptide dissertation zeigten S. aureus-Mutanten, denen die RND Efflux Pumpe SecDF gänzlich fehlt oder funktionell deletiert wurde, ebenfalls im Vergleich zu ihrem SecDF-positiven Ausgangsstamm und einer SecDF-komplementierten Mutante signifikant niedrigere MHKs für CAP18 und für BMAP Für die restlichen Cathelicidine konnte dieser Phänotyp nicht beobachtet werden. Da Cathelicidine eine Schlüsselrolle in der Abwehr von bakteriellen Infektionen durch Neutrophile spielen, wurde im letzten Teil der These untersucht, ob die Efflux Pumpe SecDF zusätzlich antimikrobielle peptide dissertation Veränderung der in vitro AMP-MHKs auch einen Einfluss auf die antimikrobiellen Aktivitäten von Neutrophilen hat Kapitel 6.

Hierfür wurde humanes und bovines Blut, sowie antimikrobielle peptide dissertation Neutrophile mit einem SecDF-tragenden Wildtyp WT Stamm, einem SecDF-defizienten Stamm und einem SecDF-komplementierten Stamm infiziert und das Überleben der Bakterien ermittelt. Der Stamm ohne SecDF zeigte eine höhere Überlebensfähigkeit in Anwesenheit von humanem Blut und bovinen Neutrophilen.

Die Ursachen, die dieser Beobachtung zugrunde liegen, müssen jedoch in weiteren Studien geklärt werden. Diese Daten deuten darauf hin, dass SecDF das Überleben von S. aureus in humanem Blut und in Gegenwart von bovinen Neutrophilen beeinflusst. Zusammenfassend zeigen diese Ergebnisse spezies-spezifische Unterschiede in der Interaktion von Cathelicidinen mit S.

aureus, besonders im Hinblick antimikrobielle peptide dissertation die Aktivität der bakteriellen Efflux Pumpe SecDF. Da ferner die getesteten Resistenzgene keinen Einfluss auf die Wirkung der getesteten AMPs haben, könnte der Einsatz von AMPs bei multi-resistenten S, antimikrobielle peptide dissertation. aureus-Isolaten eine vielversprechende Behandlungsalternative antimikrobielle peptide dissertation. urn:nbn:de:gbv copy citation link.

Thesis Antimikrobielle peptide dissertation effect of antimicrobial peptides on the innate host responses against Dissertation All rights reserved published. Blodkamp, Stefanie. English German Staphylococcus aureus is an important zoonotic pathogen, antimikrobielle peptide dissertationwhich can cause various diseases in humans and animals.

Aktionen save as Zip. add to list Actions To edit the document, please log in. Citation style: ACS American Chemical Society AMA American Medical Association APA American Psychological Association Chicago CSE Council of Science Editors DIN ISO NLN National Library of Medicine. copy citation link, antimikrobielle peptide dissertation. version history. Antimikrobielle Antimikrobielle peptide dissertation Dissertation or with any other assignments, it is no problem for us.

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Immunology - Antimicrobial Peptides

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