Institut für Molekulare Infektionsbiologie
Refine
Has Fulltext
- yes (33)
Is part of the Bibliography
- yes (33)
Year of publication
Document Type
- Doctoral Thesis (33)
Keywords
- Candida albicans (6)
- Escherichia coli (5)
- Malaria (3)
- Proteasen (3)
- Resistenz (3)
- Aspergillus fumigatus (2)
- Bacteria (2)
- Dendritische Zelle (2)
- E. coli Nissle 1917 (2)
- Enterobacteriaceae (2)
- Fluconazol (2)
- Fluconazole (2)
- Genexpression (2)
- Leishmania major (2)
- Plasmodium falciparum (2)
- Probiotikum (2)
- RNA (2)
- Small RNA (2)
- Staphylococcus aureus (2)
- 3D Gewebemodelle (1)
- 3D cell culture (1)
- 3D tissue model (1)
- Adhärenz (1)
- Adhäsion (1)
- Antibiotic (1)
- Antibiotikum (1)
- Antikörper-Antwort (1)
- Antimicrobial activity (1)
- Antimykotikum (1)
- Arzneimitteldesign (1)
- Aspartatprotease (1)
- Autotransporter (1)
- Autotransporterprotein (1)
- Bacterial infection (1)
- Bakterielle Infektion (1)
- Bakterien (1)
- Biofilm (1)
- Biofilm formation (1)
- Bioinformatics (1)
- Biosynthese der aromatischen Aminosäuren (1)
- Bovine Mastitis (1)
- CDR1-Effluxpumpe (1)
- Campylobacter jejuni (1)
- Characterization (1)
- Complexome (1)
- Cyanobacteria (1)
- Cyanobakterien (1)
- Cysteinproteasen (1)
- Defensine (1)
- Denaturierende Gradienten-Gelelektrophorese (1)
- Denaturing Gradient Gel Electrophoresis (1)
- Dendritic cell (1)
- Drug resistance (1)
- Dual RNA-seq (1)
- E.coli Nissle 1917 (1)
- Efflux pump (1)
- Effluxpumpen (1)
- Evolution (1)
- Fitness (1)
- Flagelle (1)
- Fusobacterium nucleatum (1)
- Gametogenese (1)
- Gametozyt (1)
- Geißel <Biologie> (1)
- Genomik (1)
- Glykosylierung (1)
- Glykosyltransferase (1)
- Grad-seq (1)
- HBD2 (1)
- HD5 (1)
- HIV (1)
- Harnwegsinfektion (1)
- Hidden-Markov-Modell (1)
- Histatin 5 (1)
- Hospitalismus <Hygiene> (1)
- Human-pathogenic (1)
- IL-4 (1)
- IL-4 Rezeptor alpha (1)
- IL-4 receptor alpha chain (1)
- Immunisierung (1)
- Immunologie (1)
- Immunotherapy (1)
- Immunsystem (1)
- Impfung (1)
- Infection models (1)
- Interferon <gamma-> (1)
- Interleukin 12 (1)
- Isolation and Characterization (1)
- Kleine Proteine (1)
- Komplement <Immunologie> (1)
- Leishmania (1)
- Library of Phytochemicals (1)
- Library of plant species (1)
- MDR1 (1)
- MET-T-box riboswitch (1)
- MRR1 (1)
- MRSA (1)
- MT02 (1)
- Makrophage (1)
- Malaria tropica (1)
- Meeresschwämme (1)
- Metalloprotease (1)
- Methioninbiosynthese (1)
- MgrB (1)
- MicF (1)
- Microarray (1)
- Microscopy (1)
- Microwave Assisted Extraction (1)
- Mikroskopie (1)
- Mrr1 (1)
- Multidrugresistant (1)
- Multiproteinkomplex (1)
- Nanotubes (1)
- Naphthalinderivate (1)
- Nature-Insipired Synthesis (1)
- Nitrogen (1)
- Non-coding RNA (1)
- Nosocomial Infections (1)
- Nosokomiale Infektionen (1)
- Oberflächenproteine der Sexualstadien (1)
- Pathogene Bakterien (1)
- Pathogens (1)
- Pathologie (1)
- Pathology (1)
- Pflanzen (1)
- Plant extracts (1)
- Plants (1)
- Polysaccharide intercellular adhesin (PIA) (1)
- Porifera (1)
- Posttranskriptionelle Regulation (1)
- Probiotic (1)
- Proteaseinhibitor (1)
- Proteases (1)
- Proteine (1)
- Proteolyse (1)
- Proteolysis (1)
- Quartäre Bisnaphthalimide (1)
- Quaternary Bisnaphthalimide (1)
- RNA Abbau (1)
- RNA decay (1)
- RNA-binding protein (1)
- RNS (1)
- RNS-Bindungsproteine (1)
- Recombinant defensins (1)
- Regulation (1)
- Rekombinante DNS (1)
- Reproducibility challenges (1)
- Resistance (1)
- Resistenzmechanismen (1)
- SAP2 (1)
- STEC (1)
- STP1 (1)
- Salmonella (1)
- Salmonella Typhimurium (1)
- Salmonella enterica (1)
- Schwamm (1)
- Secretion (1)
- Sequence Analysis (1)
- Sequenzanalyse (1)
- Serinprotease (1)
- Sexuelle Entwicklung (1)
- Sponge diseases (1)
- Staphylococcus (1)
- Staphylococcus epidermidis (1)
- Stickstoff (1)
- Stickstoffmetabolismus (1)
- Stickstoffwechsel (1)
- Streptococcus pneumoniae (1)
- Symbionts (1)
- Symbiose (1)
- Synthese (1)
- Synthesis (1)
- Thiostrepton (1)
- Tissue Engineering (1)
- TraDIS (1)
- Transkription <Genetik> (1)
- Transkriptionsfaktor (1)
- Transkriptomanalyse (1)
- Transmissionsblockierende Impfstoffe (1)
- UPEC (1)
- Vakuole (1)
- Virulenz (1)
- Virulenzfaktor (1)
- Wirtszelle (1)
- Yeast (1)
- Zellfilamente (1)
- Zink-Cluster-Transkriptionsfaktoren (1)
- Zink-Finger-Proteine (1)
- adhesion (1)
- ammonium (1)
- aromatic amino acid biosynthesis (1)
- artifizielle Aktivierung (1)
- aspartic protease (1)
- autotransporter (1)
- bac-genomics-scripts (1)
- candida (1)
- candida albicans (1)
- cell filaments (1)
- cell wall (1)
- co-infection (1)
- dendritic cells (1)
- diagnostic Microarray (1)
- diagnostischer Microarray (1)
- drug (1)
- dual RNA-seq (1)
- ecoli_VF_collection (1)
- efflux pump (1)
- entero-aggregative-haemorrhagic Escherichia coli (EAHEC) (1)
- flagellum (1)
- fungus (1)
- gametocyte (1)
- genetic modification (1)
- high-throughput sequencing (1)
- host colonization (1)
- human factor H (1)
- humaner Faktor H (1)
- hybrid (1)
- icaADBC (1)
- infection biology (1)
- kinase (1)
- malaria (1)
- mastitis-associated Escherichia coli (MAEC) (1)
- metallo protease (1)
- methionine biosynthesis (1)
- murine leishmaniasis (1)
- murines Modell der aufsteigenden Harnwegsinfektion (1)
- nanotubes (1)
- ncRNA (1)
- non-coding RNA (1)
- oligopeptide transport (1)
- pathotypes (1)
- peptide (1)
- phylogeny (1)
- posttranscriptional regulation (1)
- protease (1)
- protease inhibitor (1)
- proteasome (1)
- regulatory RNA (1)
- resistance (1)
- riboswitch (1)
- screening (1)
- serine protease (1)
- sexual stage surface proteins (1)
- sigma factor (1)
- small proteins (1)
- thiostrepton (1)
- transcription regulator (1)
- transmission blocking vaccine (1)
- transport (1)
- vaccine (1)
- vacuole (1)
- virulence factors (1)
- yeast (1)
Institute
- Graduate School of Life Sciences (33) (remove)
Sonstige beteiligte Institutionen
Nitrogen-regulated pathogenesis describes the expression of virulence attributes as direct response to the quantity and quality of an available nitrogen source. As consequence of nitrogen availability, the opportunistic human fungal pathogen Candida albicans changes its morphology and secretes aspartic proteases [SAPs], both well characterized virulence attributes. C. albicans, contrarily to its normally non-pathogenic relative Saccharomyces cerevisiae, is able to utilize proteins, which are considered as abundant and important nitrogen source within the human host. To assimilate complex proteinaceous matter, extracellular proteolysis is followed by uptake of the degradation products through dedicated peptide transporters (di-/tripeptide transporters [PTRs] and oligopeptide transporters [OPTs]). The expression of both traits is transcriptionally controlled by Stp1 - the global regulator of protein utilization - in C. albicans. The aim of the present study was to elucidate the regulation of virulence attributes of the pathogenic fungus C. albicans by nitrogen availability in more detail. Within a genome wide binding profile of Stp1, during growth with proteins, more than 600 Stp1 target genes were identified, thereby confirming its role in the usage of proteins, but also other nitrogenous compounds as nitrogen source. Moreover, the revealed targets suggest an involvement of Stp1 in the general adaption to nutrient availability as well as in the environmental stress response. With the focus on protein utilization and nitrogen-regulated pathogenesis, the regulation of the major secreted aspartic protease Sap2 - additionally one of the prime examples of allelic heterogeneity in C. albicans - was investigated in detail. Thereby, the heterogezygous SAP2 promoter helped to identify an unintended genomic alteration as the true cause of a growth defect of a C. albicans mutant. Additionally, the promoter region, which was responsible for the differential activation of the SAP2 alleles, was delimited. Furthermore, general Sap2 induction was demonstrated to be mediated by distinct cis-acting elements that are required for a high or a low activity of SAP2 expression. For the utilization of proteins as nitrogen source it is also crucial to take up the peptides that are produced by extracellular proteolysis. Therefore, the function and importance of specific peptide transporters was investigated in C. albicans mutants, unable to use peptides as nitrogen source (opt1Δ/Δ opt2Δ/Δ opt3Δ/Δ opt4Δ/Δ opt5Δ/Δ ptr2Δ/Δ ptr22Δ/Δ septuple null mutants). The overexpression of individual transporters in these mutants revealed differential substrate specificities and expanded the specificity of the OPTs to dipeptides, a completely new facet of these transporters. The peptide-uptake deficient mutants were further used to elucidate, whether indeed proteins and peptides are an important in vivo nitrogen source for C. albicans. It was found that during competitive colonization of the mouse intestine these mutants exhibited wild-type fitness, indicating that neither proteins nor peptides are primary nitrogen sources required to efficiently support growth of C. albicans in the mouse gut. Adequate availability of the preferred nitrogen source ammonium represses the utilization of proteins and other alternative nitrogen sources, but also the expression of virulence attributes, like Sap secretion and nitrogen-starvation induced filamentation. In order to discriminate, whether ammonium availability is externally sensed or determined inside the cell by C. albicans, the response to exterior ammonium concentrations of ammonium-uptake deficient mutants (mep1Δ/Δ mep2Δ/Δ null mutants) was investigated. This study showed that presence of an otherwise suppressing ammonium concentration did not inhibit Sap2 proteases secretion and arginine-induced filamentation in these mutants. Conclusively, ammonium availability is primarily determined inside the cell in order to control the expression of virulence traits. In sum, the present work contributes to the current understanding of how C. albicans regulates expression of virulence-associated traits in response to the presence of available nitrogen sources - especially proteins and peptides - in order to adapt its lifestyle within a human host.