Refine
Has Fulltext
- yes (22) (remove)
Is part of the Bibliography
- yes (22)
Year of publication
- 2013 (22) (remove)
Document Type
- Journal article (19)
- Doctoral Thesis (3)
Keywords
- expression (3)
- Candida albicans (2)
- DNA transcription (2)
- gene (2)
- in vivo imaging (2)
- in-vivo (2)
- magnetic resonance imaging (2)
- methionine (2)
- staphylococcus aureus (2)
- transcription factors (2)
- transmission (2)
- 2-component system (1)
- Anopheles stephensi (1)
- Antimykotikum (1)
- CDR1-Effluxpumpe (1)
- CRISPRs (1)
- CUL4-DDB1 ubiquitin ligase (1)
- DNA methylferase homolog (1)
- Fluconazol (1)
- Ileal Crohns-disease (1)
- Krankheitsübertragung (1)
- Lung cancer (1)
- Lungenkrebs (1)
- MI-2/NURD complex (1)
- Malaria (1)
- Malariamücke (1)
- Malignant effusion (1)
- Mitteldarm (1)
- Molekulare Infektionsbiologie (1)
- Mosquito (1)
- Mücke (1)
- N-glycans (1)
- NF-KAPPA-B (1)
- NRG1 (1)
- Nitrogen (1)
- Oncolytic virotherapy (1)
- Proteasen (1)
- Proteine (1)
- RNA synthesis (1)
- Regulation (1)
- Resistenz (1)
- Resistenzmechanismen (1)
- SAP2 (1)
- STP1 (1)
- Stickstoff (1)
- T cells (1)
- TRNA(ASP) (1)
- UME6 (1)
- VEGF (1)
- Vascular endothelial Growth Factor (1)
- Virulenz (1)
- Zink-Cluster-Transkriptionsfaktoren (1)
- Zink-Finger-Proteine (1)
- abscesses (1)
- activation (1)
- allelic replacement (1)
- alpha defensins (1)
- ammonium (1)
- anti-sigma factor (1)
- antibiotics (1)
- antibodies (1)
- antigen (1)
- antimicrobial peptides (1)
- artifizielle Aktivierung (1)
- aspergillus fumigatus (1)
- bacillus subtilis (1)
- bacterial genomics (1)
- balancing selection (1)
- binding (1)
- biofilms (1)
- bioluminescence imaging (1)
- biosynthesis (1)
- campylobacter (1)
- cancer (1)
- candida albicans (1)
- carcinoma (1)
- cell-cycle arrest (1)
- coli nissel 1917 (1)
- colorectal (1)
- colorectal cancer (1)
- conservation (1)
- conserving surgery (1)
- cytokines (1)
- drospophila (1)
- emulsions (1)
- enzyme APOBEC3G (1)
- epidemiology (1)
- escherichia coli (1)
- falciparum (1)
- fluorescence imaging (1)
- fluorescence microscopy (1)
- fungal pathogens (1)
- gene expression (1)
- gene regulation (1)
- genome annotation (1)
- genome sequence (1)
- genome-wide analysis (1)
- genomic libraries (1)
- genomic library construction (1)
- growth (1)
- histology (1)
- host-cell invasion (1)
- identification (1)
- immune response (1)
- immunodeficiency-virus type-1 (1)
- infection (1)
- inflammation (1)
- inflammatory-bowel-disease (1)
- leishmania major (1)
- library screening (1)
- locus (1)
- lymph nodes (1)
- macrophage infection (1)
- macrophages (1)
- malaria vaccine (1)
- mass spectrometry (1)
- mastectomy (1)
- mechanism (1)
- metastases (1)
- metastasis (1)
- midgut (1)
- morphogenesis (1)
- mouse models (1)
- oncolytic virotherapy (1)
- oncolytic viruses (1)
- parasitic diseases (1)
- peptide (1)
- pheromones (1)
- photooxidative stress (1)
- photosynthesis genes (1)
- porphyromonas gingivalis (1)
- protease (1)
- protein expressions (1)
- protein kinase signaling cascade (1)
- quanititative proteomics (1)
- radiation-therapy (1)
- regulator (1)
- regulator genes (1)
- rhodobacter sphaeroides (1)
- ribonucleases (1)
- secretion (1)
- sequence motif analysis (1)
- singlet oxygen stress (1)
- sodium-iodide symporter (1)
- stage-i (1)
- staib agar (1)
- staphylococcus (1)
- stem cells (1)
- strain Newman (1)
- sulfates (1)
- sulfur (1)
- thyroid-cancer (1)
- tobacco (1)
- transcription (1)
- transcriptome analysis (1)
- transfer RNA (1)
- transport (1)
- ulcreative colitis (1)
- vaccinia virus (1)
- vancomycin (1)
- viral protein-R (1)
- virulence (1)
Institute
- Institut für Molekulare Infektionsbiologie (22) (remove)
Sonstige beteiligte Institutionen
- Genelux Corporation, San Diego Science Center, 3030 Bunker Hill Street, Suite 310, San Diego, California 92109, USA (1)
- MRB Forschungszentrum für Magnet-Resonanz-Bayern e.V., Am Hubland, D-97074 Würzburg (1)
- Research Center for Infectious Diseases (ZINF), University of Wuerzburg, Wuerzburg, Germany, (1)
Depending on the environmental conditions, the pathogenic yeast Candida albicans can undergo different developmental programs, which are controlled by dedicated transcription factors and upstream signaling pathways. C. albicans strains that are homozygous at the mating type locus can switch from the normal yeast form (white) to an elongated cell type (opaque), which is the mating-competent form of this fungus. Both white and opaque cells use the Ste11-Hst7-Cek1/Cek2 MAP kinase signaling pathway to react to the presence of mating pheromone. However, while opaque cells employ the transcription factor Cph1 to induce the mating response, white cells recruit a different downstream transcription factor, Tec1, to promote the formation of a biofilm that facilitates mating of opaque cells in the population. The switch from the white to the opaque cell form is itself induced by environmental signals that result in the upregulation of the transcription factor Wor1, the master regulator of white-opaque switching. To get insight into the upstream signaling pathways controlling the switch, we expressed all C. albicans protein kinases from a tetracycline-inducible promoter in a switching-competent strain. Screening of this library of strains showed that a hyperactive form of Ste11 lacking its N-terminal domain (Ste11ΔN467) efficiently stimulated white cells to switch to the opaque phase, a behavior that did not occur in response to pheromone. Ste11ΔN467-induced switching specifically required the downstream MAP kinase Cek1 and its target transcription factor Cph1, but not Cek2 and Tec1, and forced expression of Cph1 also promoted white-opaque switching in a Wor1-dependent manner. Therefore, depending on the activation mechanism, components of the pheromone-responsive MAP kinase pathway can be reconnected to stimulate an alternative developmental program, switching of white cells to the mating-competent opaque phase.
Background
The emergence of antibiotic resistant bacteria in recent decades has highlighted the importance of developing new drugs to treat infections. However, in addition to the design of new drugs, the development of accurate preclinical testing methods is essential. In vivo imaging technologies such as bioluminescence imaging (BLI) or magnetic resonance imaging (MRI) are promising approaches. In a previous study, we showed the effectiveness of \(^{19}\)F MRI using perfluorocarbon (PFC) emulsions for detecting the site of Staphylococcus aureus infection. In the present follow-up study, we investigated the use of this method for in vivo visualization of the effects of antibiotic therapy.
Methods/Principal findings
Mice were infected with S. aureus Xen29 and treated with 0.9% NaCl solution, vancomycin or linezolid. Mock treatment led to the highest bioluminescence values during infection followed by vancomycin treatment. Counting the number of colony-forming units (cfu) at 7 days post-infection (p.i.) showed the highest bacterial burden for the mock group and the lowest for the linezolid group. Administration of PFCs at day 2 p.i. led to the accumulation of \(^{19}\)F at the rim of the abscess in all mice (in the shape of a hollow sphere), and antibiotic treatment decreased the \(^{19}\)F signal intensity and volume. Linezolid showed the strongest effect. The BLI, cfu, and MRI results were comparable.
Conclusions
\(^{19}\)F-MRI with PFCs is an effective non-invasive method for assessing the effects of antibiotic therapy in vivo. This method does not depend on pathogen specific markers and can therefore be used to estimate the efficacy of antibacterial therapy against a broad range of clinically relevant pathogens, and to localize sites of infection.