Refine
Has Fulltext
- yes (289)
Is part of the Bibliography
- yes (289)
Year of publication
Document Type
- Journal article (289) (remove)
Language
- English (289) (remove)
Keywords
- Infektionsbiologie (57)
- Escherichia coli (19)
- Candida albicans (12)
- escherichia coli (11)
- gene expression (10)
- RNA-seq (9)
- expression (8)
- infection (8)
- Biologie (7)
- Staphylococcus aureus (7)
- virulence (7)
- Immunologie (6)
- epithelial cells (6)
- identification (6)
- activation (5)
- antimicrobial resistance (5)
- gene regulation (5)
- messenger RNA (5)
- plasmodium falciparum (5)
- sRNA (5)
- transcriptome (5)
- antibiotics (4)
- antibodies (4)
- antisense RNA (4)
- bacteria (4)
- biofilms (4)
- inhibition (4)
- pathogens (4)
- resistance (4)
- small RNA (4)
- synthesis (4)
- transcriptomics (4)
- vancomycin (4)
- Expression (3)
- Hfq (3)
- Legionella pneumophila (3)
- Neisseria meningitidis (3)
- RNA (3)
- RNA sequencing (3)
- RNA-binding proteins (3)
- Salmonella (3)
- adaptation (3)
- antibacterial activity (3)
- autophagy (3)
- bacillus subtilis (3)
- biology (3)
- cancer (3)
- genes (3)
- genome sequence (3)
- leishmania major (3)
- macrophages (3)
- mechanisms (3)
- medicine (3)
- mouse models (3)
- protein kinase (3)
- sequence (3)
- signaling pathway (3)
- staphylococcus aureus (3)
- stem cells (3)
- substituent (3)
- transcription (3)
- transcription factors (3)
- translation (3)
- Agent (2)
- Antisense RNA (2)
- Aspergillus fumigatus (2)
- Breast-tumors (2)
- COVID-19 (2)
- Campylobacter jejuni (2)
- Cancer (2)
- Candida auris (2)
- DNA transcription (2)
- E. coli serotype 06 (2)
- F8 fimbriae (2)
- Grad-seq (2)
- Growth (2)
- HFQ (2)
- HeLa cells (2)
- Helicobacter pylori (2)
- In-vivo (2)
- Leishmania (2)
- Lung cancer (2)
- MATQ-seq (2)
- Medizin (2)
- Nude-mice (2)
- RNA synthesis (2)
- RNS (2)
- Rhodobacter sphaeroides (2)
- SARS-CoV-2 (2)
- SEQ (2)
- Salmonella Typhimurium (2)
- Salmonella enterica (2)
- Salmonella typhimurium (2)
- Salmonellosis (2)
- Streptomyces (2)
- Therapy (2)
- adhesion (2)
- allelic replacement (2)
- antibiotic resistance (2)
- antifungals (2)
- antigen (2)
- antisense RNAs (2)
- apoptosis (2)
- archaea (2)
- bacterial genetics (2)
- bioluminescence imaging (2)
- biosynthesis (2)
- chaperone (2)
- comparative genomics (2)
- cytokines (2)
- cytotoxicity (2)
- dRNA-Seq (2)
- enterica serovar typhimurium (2)
- epidemiology (2)
- evolution (2)
- fluorescence microscopy (2)
- gastric cancer (2)
- gastrointestinal tract (2)
- gene (2)
- gene cloning (2)
- gene expression profiling (2)
- genome (2)
- genome annotation (2)
- glycopeptide antibiotics (2)
- hemolysin (2)
- host cells (2)
- in vitro (2)
- in vivo imaging (2)
- in-vitro (2)
- in-vivo (2)
- inflammation (2)
- inhibitor (2)
- leishmaniasis (2)
- liraglutide (2)
- magnetic resonance imaging (2)
- malaria (2)
- mechanism (2)
- messenger-RNA (2)
- metabolism (2)
- metastasis (2)
- methionine (2)
- mutation (2)
- neuroimmunology (2)
- neutrophils (2)
- noncoding RNA (2)
- obesity (2)
- oncolytic virotherapy (2)
- oncolytic viruses (2)
- parasitic diseases (2)
- pathogenicity (2)
- plants (2)
- polycationic peptides (2)
- protein kinases (2)
- proteins (2)
- recombination (2)
- red fluorescent protein (2)
- regulator (2)
- regulator genes (2)
- regulatory RNA (2)
- response regulator (2)
- responses (2)
- ribonucleases (2)
- riboswitch (2)
- secretion (2)
- secretion systems (2)
- signal transduction (2)
- single-cell RNA-seq (2)
- small RNAs (2)
- small nucleolar RNAs (2)
- strains (2)
- structure-activity (2)
- subunit (2)
- therapy (2)
- transmission (2)
- transmission electron microscopy (2)
- tumors (2)
- type VII secretion system (2)
- vaccinia virus (2)
- virulence factors (2)
- (+)-limonene (1)
- (Nucleotide sequence (1)
- 0 antigen (1)
- 2-component system (1)
- 3D tissue model (1)
- 3′ UTR (1)
- 5-bromodeoxyuridine (1)
- 6S RNA (1)
- AMP-activated kinases (1)
- ATG (1)
- ATG8 (1)
- AcrAB-TolC efflux pump (1)
- Adherence (1)
- Adhesion (1)
- Adhäsion (1)
- Alkyltransferase Ribozyme SAMURI (1)
- Apicomplexan (1)
- Archaea (1)
- Avirulent Salmonella (1)
- BNIP3 (1)
- BT_1884 (1)
- Bacillus subtilis (1)
- Bacterial conjugation (1)
- Bacterial pathogens (1)
- Bacteriaophage AR9 (1)
- Bakterien (1)
- Biology (1)
- Blood-brain barrier (1)
- Bordeiella pertussis (1)
- Bovis (1)
- Bradyrhizobium (1)
- C-6-H (1)
- C-Terminus (1)
- COX-2 (1)
- CRISPR-Cas system (1)
- CRISPRs (1)
- CTSE (1)
- CUL4-DDB1 ubiquitin ligase (1)
- Carcinoma (1)
- Cas9 (1)
- Cell binding (1)
- Chemical modification (1)
- Chemotherapy (1)
- Combination therapy (1)
- Crohns-disease (1)
- CsrA (1)
- Cutaneous leishmaniasis (1)
- Cyclophosphamide (1)
- Cystic-fibriosis (1)
- DASH (1)
- DNA (1)
- DNA glycosation (1)
- DNA lang range mapping (1)
- DNA methylation (1)
- DNA methylferase homolog (1)
- Deletion (1)
- Dextran sulphate (1)
- Diarrhea (1)
- Disease gene prioritization (1)
- Division (1)
- Dual 3'seq (1)
- E. coli hemolysin (1)
- E. coli virulence (1)
- ESAT‐6‐like secretion system (1)
- ESS (1)
- Elektronisches Publizieren (1)
- Enterica serovar typhimurium (1)
- Enterobacteriaceae (1)
- Enterococcus faecalis (1)
- Enterococcus faecium (1)
- Environmental isolate (1)
- Epstein-Barr virus (1)
- Erwachsener (1)
- Erwinia amylovora (1)
- EsaA (1)
- Escherichia coli-Hfq (1)
- Escherichia-coli K-12 (1)
- Ethiopia (1)
- Evolution (1)
- Excision (1)
- F-19 MRI (1)
- F1 (1)
- Family (1)
- Fimbria (1)
- Fimbriae (1)
- FinO family (1)
- Foc protein (1)
- Ftsz (1)
- GFP (1)
- GI-101A tumor xenografts (1)
- GLP-1 (1)
- GLV-1 h153 (1)
- GLV-1H68 (1)
- GO1 (1)
- Gene (1)
- Gene cloning (1)
- Gene expression (1)
- Gene mapping (1)
- Gene regulation (1)
- Gene-expression (1)
- Gene-transfer (1)
- Genetik (1)
- Genome analysis (1)
- Genome re-annotation (1)
- Genomic profile (1)
- Germany (1)
- GibS (1)
- Gifsy-1 (1)
- Gram-positive bacteria (1)
- Haemolysin (1)
- Haloferax volcanii (1)
- Harnwegsinfekt (1)
- Helicobacterpylori (1)
- Hemolysin excretion (1)
- Hirnhautentzündung (1)
- Homology (1)
- Hospital water system (1)
- Host adaptation (1)
- Host cells (1)
- Hämolysin (1)
- IL-12 production (1)
- IcaR (1)
- Ileal Crohns-disease (1)
- Images (1)
- In-vitro (1)
- Inactivation (1)
- Infection (1)
- Inflammation (1)
- Inhibitor (1)
- Internal transcription start site (1)
- Invasion genes (1)
- Ire1 (1)
- Iron-oxide (1)
- Iron-uptake (1)
- IsrK (1)
- K279a (1)
- KhpB protein (1)
- Klebsiella pneumoniae (1)
- Krebs <Medizin> (1)
- Langerhans cell (1)
- Leaderless transcript (1)
- Legionella ssp. (1)
- Legionellae (1)
- Leishmania major (1)
- Lesions (1)
- Level (1)
- Listeria monocytogenes (1)
- Lungenkrebs (1)
- Lysis (medicine) (1)
- MACE (1)
- MI-2/NURD complex (1)
- MRI reporter (1)
- MRSA (1)
- MRSA - methicillin-resistant Staphylococcus aureus (1)
- MTOR (1)
- MVT (1)
- Macrophage (1)
- Maintenance (1)
- Malaria (1)
- Malignant effusion (1)
- Medicine (1)
- Methanosarcina mazei (1)
- Mice (1)
- MicroRNAs (1)
- Mig1 (1)
- Minor subunits (1)
- Molekulare Infektionsbiologie (1)
- Mouse (1)
- Mutant (1)
- Mycobacterium (1)
- N-glycans (1)
- NAFLD (1)
- NAS (1)
- NASH (1)
- ND10 complex (1)
- NF-KAPPA-B (1)
- NK cells (1)
- NOTCH (1)
- NRG1 (1)
- NSG (1)
- Neugeborenes (1)
- Nodule (1)
- Non-coding RNAs (1)
- Nonpathogenic Escherichia-coli (1)
- OLFM4 (1)
- Oncolytic virotherapy (1)
- One Health (1)
- Organoids (1)
- Orthogonal field attenuation gel electrophoresis (1)
- OxyR (1)
- P-fimbriae (1)
- P. falciparum (1)
- PCR (1)
- PEGylation (1)
- PETRI-seq (1)
- PFS25 (1)
- PIA/ica (1)
- PML (1)
- PML nuclear-bodies (1)
- PPGPP (1)
- PSI-blast (1)
- PYY3-36 (1)
- Paeonia (1)
- Pan1 (1)
- Parkinson's disease (1)
- Particles (1)
- Pathogenicity (1)
- Pathogens (1)
- PfAMA1 (1)
- PfCCp protein (1)
- Pfs230 (1)
- Pilus (1)
- PknB (1)
- Plasmid (1)
- ProQ (1)
- Promoter (1)
- Promoter prediction (1)
- Protein (1)
- Protein function prediction (1)
- Proteins (1)
- Proteogenomics (1)
- Proteomanalyse (1)
- Pseudomonas (1)
- Pseudomonas aeruginosa (1)
- Pseudomonas-aeruginosa (1)
- RFP (1)
- RNA CHAPERONE HFQ (1)
- RNA chaperone Hfq (1)
- RNA denaturation (1)
- RNA expression (1)
- RNA sequence analyses (1)
- RNA structure (1)
- RNA-Seq (1)
- RNA-polymerase-I (1)
- RNA-polymerase-II (1)
- RNA-sequencing (1)
- RNAseq (1)
- RNase E (1)
- RNase III (1)
- ROS (1)
- RTS,S/AS01 malaria vaccine (1)
- RYGB (1)
- Rapid evolution (1)
- Rats (1)
- Recombinant vaccinia (1)
- Recombination directionality factor (1)
- Regression (1)
- Ribosome profiling (1)
- Roux-en-Y gastric bypass surgery (1)
- S fimbrial adhesin (Sfa) (1)
- S-Fimbriae (1)
- S-fimbria (1)
- S-fimbriae (1)
- S. aureus (1)
- SER/THR kinase (1)
- SM-like protein (1)
- SNF1 (1)
- SUBSP carotovora (1)
- SWI2/SNF2-like protein (1)
- Salmonella enterica Typhimurium strain SL1344 (1)
- Salmonella-enteritidis (1)
- Salmonella-typhimurium (1)
- Schistosoma japonicum; Egg antigen; Carbohydrate epitope; Circumoval precipitin test; Immunoassay (1)
- SdsR (1)
- Sequence identity (1)
- Sequencing (1)
- Serogroup (1)
- Serratia marcescens (1)
- Shiga toxin-producing Escherichia coli (1)
- Shigella (1)
- Shigellosis (1)
- Site-specific RNA labelling (1)
- Snf1 (1)
- Soft-tissue infection (1)
- Southern hybridization (1)
- Speichel (1)
- Staphylococcal infection (1)
- Staphylococcus aureus USA300 (1)
- Staphylococcus-aureus (1)
- Stenotrophomonas maltophilia (1)
- Stp (1)
- Strain nissle-1917 (1)
- Strains (1)
- Sugar-transport (1)
- Suicide vector (1)
- SuperSAGE (1)
- T cell (1)
- T cells (1)
- T helper cell (1)
- T lymphocytes (1)
- T-cell (1)
- TEM (1)
- TRNA(ASP) (1)
- Tissue (1)
- Toll-like receptors (1)
- Toxicity ; plasmids (1)
- Toxoplasma gondii (1)
- TraDIS (1)
- Tracking (1)
- Transcription (1)
- Transcription profiling (1)
- Transcription start site (1)
- Transcriptome (1)
- Transcriptome analysis (1)
- Transfer-RNA modification (1)
- Translation efficiency (1)
- Transposon insertion sequencing (1)
- Typhimurium (1)
- UKZ (1)
- UME6 (1)
- Urinary tract (1)
- Uropatbcgenie E. coli (1)
- VEGF (1)
- Vaccinia virus (1)
- Valeriana wallichii (1)
- Variability (1)
- Variants (1)
- Vascular endothelial Growth Factor (1)
- Virologie (1)
- Virulence (1)
- Virusinfektion (1)
- WD40 (1)
- Yersinia (1)
- Yersinia-pseudotuberculosis (1)
- YoelII-Nigeriensis (1)
- Ypk1 (1)
- abscesses (1)
- acetivorans C2A (1)
- acetones (1)
- acid (1)
- acrican trypanosomes (1)
- actinomycetes (1)
- activation mechanism (1)
- acute myeloid leukemia (1)
- adaptation phase (1)
- adults (1)
- agroinfiltration (1)
- alignment (1)
- alignment clustering (1)
- alpha defensins (1)
- alternative pig farming (1)
- alveolar fibrosis (1)
- alveolar regeneration (1)
- animal model (1)
- animal models (1)
- animal-model (1)
- annotation (1)
- anti-biofilm (1)
- anti-schistosomal activity (1)
- anti-sigma factor (1)
- antibacterial (1)
- antibacterial drug resistance (1)
- antibacterials (1)
- antibiotic (1)
- antibiotic production (1)
- antifungal drug (1)
- antigen-presenting cells (1)
- antigenic variation (1)
- antimicrobial activity (1)
- antimicrobial peptides (1)
- antitermination (1)
- arabidopsis (1)
- aspergillosis (1)
- aspergillus fumigatus (1)
- atypical tetracyclines (1)
- autophagy-related (1)
- azobenzenes (1)
- bacterial biofilms (1)
- bacterial genomes (1)
- bacterial genomics (1)
- bacterial immune evasion (1)
- bacterial infection (1)
- bacterial infection model (1)
- bacterial lipoproteins (1)
- bacterial migration (1)
- bacterial pathogen (1)
- bacterial resistance (1)
- bacterial secretion (1)
- bacterial signal molecule (1)
- bacterial transcription (1)
- bacterial virulence (1)
- bacteriophage (1)
- balancing selection (1)
- beta-glucuronidase (1)
- beta-lactamases (1)
- binding (1)
- binding protein HFQ (1)
- biocide polyhexamethylene biguanide (1)
- biofilm (1)
- biofilm regulation (1)
- biolog (1)
- biological scaffold (1)
- bioluminescence (1)
- bioorthogonal SAM analogue ProSeDMA (1)
- biophotonic imaging (1)
- biosynthetic gene-cluster (1)
- blood (1)
- blood-brain barrier (1)
- blood-cerebrospinal fluid barrier (1)
- blood-stream forms (1)
- brain endothelial cells (1)
- breast-tumors (1)
- broad-spectrum antibiotics (1)
- burkholderia cenocepacia (1)
- caffeic acid bornyl ester (1)
- campestris PV vesicatoria (1)
- campylobacter (1)
- cancer microenvironment (1)
- cancer treatment (1)
- cancers and neoplasms (1)
- candida albicans (1)
- carbon metabolism (1)
- carcinoma (1)
- carcinomas (1)
- carvacrol (1)
- casposon (1)
- catalytic (1)
- cell cultures (1)
- cell cycle (1)
- cell death (1)
- cell differentiation (1)
- cell fusion (1)
- cell signalling (1)
- cell vaccines (1)
- cell wall (1)
- cell wall synthesis (1)
- cell-cycle arrest (1)
- cell-line (1)
- cepedia complex (1)
- chaperone HFQ (1)
- chaperone Hfq (1)
- characterization (1)
- chelocardins (1)
- children (1)
- chlamydomonas flagella (1)
- chromosomal genes (1)
- citral (1)
- citrus (1)
- clinical (1)
- clinical isolates (1)
- clonal analysis (1)
- coagulase-negative staphylococci (1)
- cold-shock protein (1)
- coli nissel 1917 (1)
- colony morphotypes (1)
- colorectal (1)
- colorectal cancer (1)
- community settings (1)
- comparative sequence analysis (1)
- complete genome sequence (1)
- complex (1)
- components (1)
- conditional mutants (1)
- conditional promoter replacement (1)
- conservation (1)
- conserving surgery (1)
- consesus (1)
- contact lens (1)
- cost-effectiveness (1)
- crystal structure (1)
- crystal-structures (1)
- cytolethal distending toxin (1)
- dRNA-seq (1)
- dark-matter (1)
- database (1)
- decay (1)
- deep sequencing (1)
- deepSuperSAGE (1)
- deficient mice (1)
- deletion mutagenesis (1)
- dendritic cells (1)
- dependent gene-expression (1)
- dependent protein-kinase (1)
- derivatives (1)
- determines pathgenicity (1)
- diarrhea (1)
- differential (1)
- directional RNA-Seq (1)
- disease (1)
- diseases of the nervous system (1)
- dogs (1)
- domain (1)
- domain genes A3(2) (1)
- down regulation (1)
- drospophila (1)
- drug design (1)
- drug resistance evolution (1)
- drug-delivery systems (1)
- dual function (1)
- dynamic programming (1)
- eigenvector centrality (1)
- electron tomography (1)
- electrophilic stress (1)
- elements (1)
- emotional behavior (1)
- emulsions (1)
- endocytosis (1)
- endoribonuclease (1)
- energy metabolism (1)
- enteric pathogens (1)
- enterica serovar thphimurium (1)
- enterobacteria (1)
- enterococci (1)
- environment (1)
- environmental regulation (1)
- enzyme APOBEC3G (1)
- enzyme-linked immunoassays (1)
- ephitelial cells (1)
- epithelial-mesenchymal transition (1)
- epithelium (1)
- escherichia coli K-12 (1)
- essential genes (1)
- essential oils (1)
- ethanol (1)
- eugenyl cinnamate (1)
- eukaryotes (1)
- experimental visceral leishmaniasis (1)
- expression mutants (1)
- extracellular domain (1)
- extracellular enzymes (1)
- extraintestinal E. coli (1)
- extraintestinal isolates (1)
- extrapulmonary (1)
- falciparum (1)
- family (1)
- fatty acids (1)
- fibronectin-binding protein (1)
- filamentous Salmonella Typhimurium (1)
- finder using symmetrical best hits (1)
- flagellar basal body (1)
- flagellum (1)
- flotillin (1)
- flow cytometry (1)
- fluconazole resistance (1)
- fluorescence imaging (1)
- fluorescent probe (1)
- fluorescent protein (1)
- flux balance analysis (1)
- food industry (1)
- functional genomics (1)
- fungal genetics (1)
- fungal pathogens (1)
- fungi (1)
- gallotannins (1)
- gamete (1)
- gametes (1)
- gametocyte (1)
- gastric bypass (1)
- gastrointestinal infections (1)
- gene expression heterogeneity (1)
- gene family targeting (1)
- gene probes (1)
- gene therapy (1)
- gene-cloning (1)
- gene-cluster (1)
- gene-expression (1)
- general stress response (1)
- genetic organization (1)
- genetic recombination (1)
- genetic transcription (1)
- genome wide (1)
- genome-wide analysis (1)
- genomes (1)
- genomic deletions (1)
- genomic islands (1)
- genomic libraries (1)
- genomic library construction (1)
- genomics (1)
- genus Aspergillus (1)
- geometry (1)
- germination (1)
- global gene expression (1)
- glv-1h68 (1)
- glycolysis (1)
- glycosome (1)
- glycosyl phosphatidyl-inostitols. (1)
- gram-negative bacteria (1)
- green fluorescent protein (1)
- growth (1)
- growth rate control (1)
- haemoproteus-columbae (1)
- halstedii JM8 (1)
- harmonia axyridis (1)
- harmonine (1)
- hela cells (1)
- hemolytic-uremic syndrome (1)
- heterogeneity (1)
- heterologous production (1)
- heteropathogenicity (1)
- hexose transporter (1)
- hidden markov-models (1)
- histidine kinases (1)
- histology (1)
- homologs (1)
- homology search (1)
- horizontal gene transfer (1)
- hos tcells (1)
- host (1)
- host (organism) (1)
- host pathogen interaction (1)
- host-cell invasion (1)
- human herpesvirus 6 (1)
- human macrophages (1)
- human pathogenic fungi (1)
- human pathogens (1)
- human sodium iodide symporter (hNIS) (1)
- humanized mice (1)
- hydrogen regulation (1)
- hydrogen-peroxide (1)
- hyperexpression techniques (1)
- hypersensitive response (1)
- hyperthermophile (1)
- hyphae (1)
- hypothalamic gene expression (1)
- immune response (1)
- immunity (1)
- immunization (1)
- immunodeficiency-virus type-1 (1)
- in vivo (1)
- in-vitro propagation (1)
- inactivation (1)
- infectious disease (1)
- inflammatory-bowel-disease (1)
- inhibitors (1)
- insect immunity (1)
- insights (1)
- integration (1)
- interaction surfaces (1)
- interactome (1)
- interferon-gamma (1)
- intermediate host (1)
- internalization (1)
- intervention strategies (1)
- interview (1)
- intestinal enteroids (1)
- intracellular pathogen (1)
- intracellular pathogens (1)
- invasion (1)
- iron limitation (1)
- island (1)
- isolation (1)
- kingdom (1)
- latency (1)
- lead structure (1)
- leaves (1)
- legionella pneumophila (1)
- leishmania (1)
- libraries (1)
- library screening (1)
- life cycle (1)
- lines (1)
- linker influence (1)
- lipids (1)
- liquid chromatography-mass spectrometry (1)
- listeria monocytogenes (1)
- livestock-associated staphylococci (1)
- locus (1)
- luciferase (1)
- lux (1)
- lymph nodes (1)
- lymphadenitis (1)
- lytic replication (1)
- mC (1)
- mCherry (1)
- macrophage infection (1)
- malaria parasite (1)
- malaria vaccine (1)
- maps (1)
- marine sponges (1)
- mass spectrometry (1)
- mastectomy (1)
- maternal separation (1)
- mating (1)
- maturation (1)
- mechanism of resistance (1)
- mechanisms of disease (1)
- membrane (1)
- membrane proteins (1)
- membrane vesicles (1)
- membrane-protein topology (1)
- meningococcus (1)
- merozoite (1)
- messanger RNA (1)
- messenger-RNA decay (1)
- meta-analysis based orthology (1)
- metabolic adaptation (1)
- metastases (1)
- methanoarchaea (1)
- methanol methyltransferase isozymes (1)
- methanosarcina mazei GO1 (1)
- methicillin (1)
- miRNAs (1)
- microRNAs (1)
- microSPLiT (1)
- microbiology (1)
- microbiome (1)
- microenvironment (1)
- microneme (1)
- microtubule motor (1)
- mitochondria (1)
- model (1)
- modulation of virus replication (1)
- molecular epidemiology (1)
- molecular evolution (1)
- monocyte (1)
- morphogenesis (1)
- mouse (1)
- mucosal inflammation (1)
- multidrug-resistant bacteria (1)
- multivesicular tubule (1)
- mycobacterium tuberculosis (1)
- mycobacterium-tuberculosis (1)
- myelin biology and repair (1)
- myeloma (1)
- natively unstructured protein (1)
- natural antisense transcripts (1)
- natural transformation (1)
- ncRNA (1)
- necrosis-factor-alpha (1)
- neisseria gonorrhoeae (1)
- network biology (1)
- non-aureus staphylococci (1)
- noncoding RNAs (1)
- nondocing RNA (1)
- northern blotting (1)
- nosocomial pathogen (1)
- nucleotide sequence (1)
- nude-mice (1)
- nutrients (1)
- olfactomedin 4 (1)
- oligopeptides (1)
- oncolytic viral therapy (1)
- oncolytic virus (1)
- one-health approach (1)
- organic farming (1)
- organization (1)
- organohalide respiration (1)
- organoids (1)
- origin (1)
- orthology (1)
- orthology network (1)
- outbreak (1)
- outer-membrane proteins (1)
- oviedomycin (1)
- oxidative stress (1)
- pangolin (1)
- par-seqFISH (1)
- parallel evolution (1)
- parasexual recombination (1)
- parasite (1)
- parasitology (1)
- paromomycin (1)
- pathogen (1)
- pathogenesis (1)
- pathogenetic organism (1)
- pathogenic bacteria (1)
- pathogenicity island 2 (1)
- peptide conjugates (1)
- peptide tyrosine tyrosine (PYY) (1)
- peptide tyrosine tyrosine 3-36 (PYY\(_{3-36}\)) (1)
- peptido-glycan associated protein (1)
- permease (1)
- persistence (1)
- persister cells (1)
- phage (1)
- phagocytes (1)
- pharmacokinetics (1)
- phased metamorphosis (1)
- phenotypic heterogeneity (1)
- phenotypic microarray (1)
- pheromones (1)
- phosphorylation (1)
- photooxidative stress (1)
- photosynthesis genes (1)
- phototrophic growth (1)
- phylogenetic analysis (1)
- phylogenetic trees (1)
- phylogeny (1)
- phytochemicals (1)
- pig farming methods (1)
- plant-made vaccines (1)
- plant-microbe interaction (1)
- plasmid-chromosome crosstalk (1)
- plasmodium (1)
- plastid targeting (1)
- point mutation (1)
- polyadenylation sites (1)
- polycistronic transcription (1)
- polymerase chain reaction (PCR) (1)
- porphyromonas gingivalis (1)
- positive selection (1)
- post-transcriptional regulation (1)
- post-transcriptionalregulation (1)
- posttranscriptional control (1)
- ppl (1)
- pre-messenger RNA (1)
- promastigotes (1)
- promoters (1)
- prophage (1)
- proteasome (1)
- protein (1)
- protein HFQ (1)
- protein expressions (1)
- protein families database (1)
- protein kinase signaling cascade (1)
- protein synthesis (1)
- protein-RNA recognition (1)
- protozoan parasite (1)
- pseudomas aeruginosa (1)
- pulmonary (1)
- purification (1)
- pyrococcus furiosus (1)
- quanititative proteomics (1)
- quinone (1)
- rRNA depletion (1)
- radiation-therapy (1)
- radioiodine therapy (1)
- ralstonia solanacearum (1)
- rat (1)
- receptor (1)
- receptors (1)
- reciprocal best hit (1)
- recombinant proteins (1)
- regionalization and organoids (1)
- regulation (1)
- regulatory small RNAs (1)
- remote sequence conservation (1)
- replication (1)
- reporter (1)
- reporter genes (1)
- repression (1)
- reputation (1)
- resistance mechanism (1)
- resistance-breaking properties (1)
- resistant Staphylococcus-aureus (1)
- reveals (1)
- rhodobacter sphaeroides (1)
- ribosomal RNA (1)
- sRNA atlas (1)
- sRNA biogenesis (1)
- salmonella enterica (1)
- sationary phase (1)
- scaffold protein (1)
- schistosoma (1)
- schistosomula (1)
- scholarly publishing (1)
- scientific publishing (1)
- secondary structure (1)
- segmentation (1)
- sequence motif analysis (1)
- sequences (1)
- sequencing protocol (1)
- serotonin (1)
- serovar Typhimurium (1)
- serum resistance (1)
- sexual stage (1)
- sfaA gene) (1)
- shiga toxin (1)
- shock sigma factor (1)
- siRNAs (1)
- signal-transduction systems (1)
- simultaneous (1)
- singlet oxygen stress (1)
- sinorhizobium fredii NGR234 (1)
- skin fatty acid (1)
- small interfering RNAs (1)
- small non-coding RNAs (1)
- small noncoding RNAs (1)
- small regulatory RNAs (1)
- sodium-iodide symporter (1)
- solubility (1)
- soluble-RNA (1)
- soluble-RNAs (1)
- sortase A (1)
- specificity (1)
- spores (1)
- stability (1)
- stage-i (1)
- staib agar (1)
- staphilococci (1)
- staphylocccal infection/epidemiology (1)
- staphylococcus (1)
- stationary phase (1)
- stomach (1)
- strain (1)
- strain Newman (1)
- streptococcus pneumoniae (1)
- stress resistance (1)
- stress response (1)
- stringency (1)
- structural elucidation (1)
- structural modification (1)
- structure activity (1)
- structure-activity relationship (1)
- structure–activity (1)
- subcellular localization (1)
- subpopulation (1)
- subtilis genome (1)
- sulfates (1)
- sulfur (1)
- suppressor mutation (1)
- surgery (1)
- synthetase (1)
- tag based (1)
- tandem mass-spectra (1)
- target (1)
- target recognition (1)
- tetrachloroethene (1)
- thymyl cinnamate (1)
- thyroid-cancer (1)
- tobacco (1)
- toll-like receptor 2 (1)
- topical treatment (1)
- toxin (1)
- trans-activation (1)
- transcription factor (1)
- transcription initiation site (1)
- transcription start site (1)
- transcription start sites (1)
- transcriptional control (1)
- transcriptional landscape (1)
- transcriptional regulation (1)
- transcriptional regulator (1)
- transcriptional start site (1)
- transcriptional uni (1)
- transcriptome analysis (1)
- transcriptomeanalysis (1)
- transfer RNA (1)
- translation initiation (1)
- translational initiation (1)
- translocation (1)
- transport systems (1)
- transposable elements (1)
- transposition (1)
- tuberculosis (1)
- two-component systems (1)
- two‐component system (1)
- type III protein secretion system complex (1)
- type III secretion system pathways (1)
- tyrosine kinase (1)
- ubiquitin (1)
- ulcreative colitis (1)
- untranslated regions (1)
- urinary tract infection (1)
- urinary tract infection (UTI) (1)
- urinary-tract-infection (1)
- uropathogenic Escherichia coli (1)
- uropathogenicity (1)
- uropathogens (1)
- vaccines (1)
- vacuoles (1)
- variant surface glycoprotein (1)
- version control (1)
- vibrio parahaemolyticus (1)
- viral protein-R (1)
- viral replication (1)
- virotherapy (1)
- virulence genes (1)
- virulence modulation (1)
- virus-infection (1)
- visceral leishmaniasis (1)
- wikis (1)
- xanthomonas (1)
- xanthomonas campestris (1)
- xanthomonas maltophilia (1)
- yvcK/glmR operon (1)
- zinc cluster transcription factor (1)
- zoonotic (1)
Institute
- Institut für Molekulare Infektionsbiologie (289) (remove)
Sonstige beteiligte Institutionen
- Genelux Corporation, San Diego Science Center, 3030 Bunker Hill Street, Suite 310, San Diego, California 92109, USA (1)
- Institut für Molekulare Infektionsbiologie (MIB) der Universität Würzburg (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)
- Research Center of Infectious Diseases (ZINF) of the University of Wurzburg, Germany (1)
Background
Differential RNA-sequencing (dRNA-seq) is indispensable for determination of primary transcriptomes. However, using dRNA-seq data to map transcriptional start sites (TSSs) and promoters genome-wide is a bioinformatics challenge. We performed dRNA-seq of Bradyrhizobium japonicum USDA 110, the nitrogen-fixing symbiont of soybean, and developed algorithms to map TSSs and promoters.
Results
A specialized machine learning procedure for TSS recognition allowed us to map 15,923 TSSs: 14,360 in free-living bacteria, 4329 in symbiosis with soybean and 2766 in both conditions. Further, we provide proteomic evidence for 4090 proteins, among them 107 proteins corresponding to new genes and 178 proteins with N-termini different from the existing annotation (72 and 109 of them with TSS support, respectively). Guided by proteomics evidence, previously identified TSSs and TSSs experimentally validated here, we assign a score threshold to flag 14 % of the mapped TSSs as a class of lower confidence. However, this class of lower confidence contains valid TSSs of low-abundant transcripts. Moreover, we developed a de novo algorithm to identify promoter motifs upstream of mapped TSSs, which is publicly available, and found motifs mainly used in symbiosis (similar to RpoN-dependent promoters) or under both conditions (similar to RpoD-dependent promoters). Mapped TSSs and putative promoters, proteomic evidence and updated gene annotation were combined into an annotation file.
Conclusions
The genome-wide TSS and promoter maps along with the extended genome annotation of B. japonicum represent a valuable resource for future systems biology studies and for detailed analyses of individual non-coding transcripts and ORFs. Our data will also provide new insights into bacterial gene regulation during the agriculturally important symbiosis between rhizobia and legumes.
Microcin C (McC) is a peptide-nucleotide antibiotic produced by Escherichia coli cells harboring a plasmid-borne operon mccABCDE. The heptapeptide MccA is converted into McC by adenylation catalyzed by the MccB enzyme. Since MccA is a substrate for MccB, a mechanism that regulates the MccA/MccB ratio likely exists. Here, we show that transcription from a promoter located upstream of mccA directs the synthesis of two transcripts: a short highly abundant transcript containing the mccA ORF and a longer minor transcript containing mccA and downstream ORFs. The short transcript is generated when RNA polymerase terminates transcription at an intrinsic terminator located in the intergenic region between the mccA and mccB genes. The function of this terminator is strongly attenuated by upstream mcc sequences. Attenuation is relieved and transcription termination is induced when ribosome binds to the mccA ORF. Ribosome binding also makes the mccA RNA exceptionally stable. Together, these two effects-ribosome induced transcription termination and stabilization of the message-account for very high abundance of the mccA transcript that is essential for McC production. The general scheme appears to be evolutionary conserved as ribosome-induced transcription termination also occurs in a homologous operon from Helicobacter pylori.
A total of 36 Escherichia coli urinary tract isolates (UTI) of serotype 06, with different combinations of capsule ( K) and flagellin ( H) antigens, were analysed according to the outer membrane pattern (OMP), serum resistance properties, mannose-resistant hemagglutination using various types of erythrocytes, and also for the genetic presence and the expression of Pfimbriae. S fimbriae/F1 C fimbriae, Type 1 fimbriae, aerobactin and hemolysin. Twenty selected strains were further analysed by pulsed field gel electrophoresis (PFGE), elaborating genomic profilas by Xba I cleavage and subsequent Southern hybridization to virulence-associated DNA probes. lt could be shown that 06 UTI isolates represent a highly heterogeneaus group of strains according to the occurrence and combination of these traits. Relatedness an the genetic and the phenotypic Ievei was found for some of the strains exhibiting the same 0: K: H: F serotype. DNA Iang-range mapping further indicated some interesting features, according to the copy number and the genomic linkage of virulence genes.
Escherichia coli isolates of serotype 06: K5 are the most common causative agents of cystitis and pyelonephritis in adults. To answer the question, as to whether strains of this particular serotype represent one special clonal group, out of a collection of 34 serotype 06: K5 isolates [Zingler et al. ( 1990) Zentralbl. Bakteriol Mikrobiol Hyg [A] 274:372-381] 15 strains were selected andanalyzed in detail. The flagellar (H) antigen and the outer membrane protein (OMP) pattern were determined. Furtherserum resistance properties and the genetic presence and expression of other virulence factors, including hemolysin, aerobactin, P fimbriae, S/F1C fimbriae and type 1 fimbriae was evaluated. In~laddition the Xbalmacrorestriction pattern of ten representative isolates was elaborated and the fimbrial (F) antigentype ofthe P fimbriae was determined, to obtain the complete 0: K: H: F pattern. These analyses could clearly show that the 06: K5 isolates do not represent one clonal group. The Xbal-macrorestriction profiles were heterogeneaus and marked differences in the hybridization patterns, using virulenceassociated gene probes in Southern hybridization of long-range-separated genomic DNA, were observed among the strains. However, some of strains showed similarities in the genomic profiles, arguing for clonal groupings among the 06: K5 isolates. lnterstingly the strains grouped tagether exhibited the same fimbrial F typethat many indicate a coincidence of this phenotypic trait with clonality.
Bacteria lose or gain genetic material and through selection, new variants become fixed in the population. Here we provide the first, genome-wide example of a single bacterial strain’s evolution in different deliberately colonized patients and the surprising insight that hosts appear to personalize their microflora. By first obtaining the complete genome sequence of the prototype asymptomatic bacteriuria strain E. coli 83972 and then resequencing its descendants after therapeutic bladder colonization of different patients, we identified 34 mutations, which affected metabolic and virulence-related genes. Further transcriptome and proteome analysis proved that these genome changes altered bacterial gene expression resulting in unique adaptation patterns in each patient. Our results provide evidence that, in addition to stochastic events, adaptive bacterial evolution is driven by individual host environments. Ongoing loss of gene function supports the hypothesis that evolution towards commensalism rather than virulence is favored during asymptomatic bladder colonization.
To understand the gene regulation of an organism of interest, a comprehensive genome annotation is essential. While some features, such as coding sequences, can be computationally predicted with high accuracy based purely on the genomic sequence, others, such as promoter elements or noncoding RNAs, are harder to detect. RNA sequencing (RNA-seq) has proven to be an efficient method to identify these genomic features and to improve genome annotations. However, processing and integrating RNA-seq data in order to generate high-resolution annotations is challenging, time consuming, and requires numerous steps. We have constructed a powerful and modular tool called ANNOgesic that provides the required analyses and simplifies RNA-seq-based bacterial and archaeal genome annotation. It can integrate data from conventional RNA-seq and differential RNA-seq and predicts and annotates numerous features, including small noncoding RNAs, with high precision. The software is available under an open source license (ISCL) at https://pypi.org/project/ANNOgesic/.
Agrobacterium species are capable of interkingdom gene transfer between bacteria and plants. The genome of Agrobacterium tumefaciens consists of a circular and a linear chromosome, the At-plasmid and the Ti-plasmid, which harbors bacterial virulence genes required for tumor formation in plants. Little is known about promoter sequences and the small RNA (sRNA) repertoire of this and other α-proteobacteria. We used a differential RNA sequencing (dRNA-seq) approach to map transcriptional start sites of 388 annotated genes and operons. In addition, a total number of 228 sRNAs was revealed from all four Agrobacterium replicons. Twenty-two of these were confirmed by independent RNA gel blot analysis and several sRNAs were differentially expressed in response to growth media, growth phase, temperature or pH. One sRNA from the Ti-plasmid was massively induced under virulence conditions. The presence of 76 cis-antisense sRNAs, two of them on the reverse strand of virulence genes, suggests considerable antisense transcription in Agrobacterium. The information gained from this study provides a valuable reservoir for an in-depth understanding of sRNA-mediated regulation of the complex physiology and infection process of Agrobacterium.
Motivation:
Next generation sequencing technologies have provided us with a wealth of information on genetic variation, but predi cting the functional significance of this variation is a difficult task. While many comparative genomics studies have focused on gene flux and large scale changes, relatively little attention has been paid to quantifying the effects of single nucleotide polymorphisms and indels on protein function, particularly in bacterial genomics.
Results:
We present a hidden Markov model based approach we call delta-bitscore (DBS) for identifying orthologous proteins that have diverged at the amino acid sequence level in a way that is likely to impact biological function. We benchmark this approach with several widely used datasets and apply it to a proof-of-concept study of orthologous proteomes in an investigation of host adaptation in Salmonella enterica. We highlight the value of the method in identifying functional divergence of genes, and suggest that this tool may be a better approach than the commonly used dN/dS metric for identifying functionally significant genetic changes occurring in recently diverged organisms.
FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged as a new class of major RNA-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mRNAs from many virulence regions, but its role, if any, in bacterial pathogenesis has not been studied. Here, using a Dual RNA-seq approach to profile ProQ-dependent gene expression changes as Salmonella infects human cells, we reveal dysregulation of bacterial motility, chemotaxis, and virulence genes which is accompanied by altered MAPK (mitogen-activated protein kinase) signaling in the host. Comparison with the other major RNA chaperone in Salmonella, Hfq, reinforces the notion that these two global RNA-binding proteins work in parallel to ensure full virulence. Of newly discovered infection-associated ProQ-bound small noncoding RNAs (sRNAs), we show that the 3′UTR-derived sRNA STnc540 is capable of repressing an infection-induced magnesium transporter mRNA in a ProQ-dependent manner. Together, this comprehensive study uncovers the relevance of ProQ for Salmonella pathogenesis and highlights the importance of RNA-binding proteins in regulating bacterial virulence programs.
IMPORTANCE
The protein ProQ has recently been discovered as the centerpiece of a previously overlooked “third domain” of small RNA-mediated control of gene expression in bacteria. As in vitro work continues to reveal molecular mechanisms, it is also important to understand how ProQ affects the life cycle of bacterial pathogens as these pathogens infect eukaryotic cells. Here, we have determined how ProQ shapes Salmonella virulence and how the activities of this RNA-binding protein compare with those of Hfq, another central protein in RNA-based gene regulation in this and other bacteria. To this end, we apply global transcriptomics of pathogen and host cells during infection. In doing so, we reveal ProQ-dependent transcript changes in key virulence and host immune pathways. Moreover, we differentiate the roles of ProQ from those of Hfq during infection, for both coding and noncoding transcripts, and provide an important resource for those interested in ProQ-dependent small RNAs in enteric bacteria.
The transcriptome is a powerful proxy for the physiological state of a cell, healthy or diseased. As a result, transcriptome analysis has become a key tool in understanding the molecular changes that accompany bacterial infections of eukaryotic cells. Until recently, such transcriptomic studies have been technically limited to analyzing mRNA expression changes in either the bacterial pathogen or the infected eukaryotic host cell. However, the increasing sensitivity of high-throughput RNA sequencing now enables “dual RNA-seq” studies, simultaneously capturing all classes of coding and noncoding transcripts in both the pathogen and the host. In the five years since the concept of dual RNA-seq was introduced, the technique has been applied to a range of infection models. This has not only led to a better understanding of the physiological changes in pathogen and host during the course of an infection but has also revealed hidden molecular phenotypes of virulence-associated small noncoding RNAs that were not visible in standard infection assays. Here, we use the knowledge gained from these recent studies to suggest experimental and computational guidelines for the design of future dual RNA-seq studies. We conclude this review by discussing prospective applications of the technique.
In Staphylococcus aureus, de novo methionine biosynthesis is regulated by a unique hierarchical pathway involving stringent-response controlled CodY repression in combination with a T-box riboswitch and RNA decay. The T-box riboswitch residing in the 5′ untranslated region (met leader RNA) of the S. aureus metICFE-mdh operon controls downstream gene transcription upon interaction with uncharged methionyl-tRNA. met leader and metICFE-mdh (m)RNAs undergo RNase-mediated degradation in a process whose molecular details are poorly understood. Here we determined the secondary structure of the met leader RNA and found the element to harbor, beyond other conserved T-box riboswitch structural features, a terminator helix which is target for RNase III endoribonucleolytic cleavage. As the terminator is a thermodynamically highly stable structure, it also forms posttranscriptionally in met leader/ metICFE-mdh read-through transcripts. Cleavage by RNase III releases the met leader from metICFE-mdh mRNA and initiates RNase J-mediated degradation of the mRNA from the 5′-end. Of note, metICFE-mdh mRNA stability varies over the length of the transcript with a longer lifespan towards the 3′-end. The obtained data suggest that coordinated RNA decay represents another checkpoint in a complex regulatory network that adjusts costly methionine biosynthesis to current metabolic requirements.
Converging evidence suggests a role of serotonin (5-hydroxytryptamine, 5-HT) and tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of 5-HT synthesis in the brain, in modulating long-term, neurobiological effects of early-life adversity. Here, we aimed at further elucidating the molecular mechanisms underlying this interaction, and its consequences for socio-emotional behaviors, with a focus on anxiety and social interaction. In this study, adult, male Tph2 null mutant (Tph2\(^{-/-}\)) and heterozygous (Tph2\(^{+/-}\)) mice, and their wildtype littermates (Tph2\(^{+/+}\)) were exposed to neonatal, maternal separation (MS) and screened for behavioral changes, followed by genome-wide RNA expression and DNA methylation profiling. In Tph2\(^{-/-}\) mice, brain 5-HT deficiency profoundly affected socio-emotional behaviors, i.e., decreased avoidance of the aversive open arms in the elevated plus-maze (EPM) as well as decreased prosocial and increased rule breaking behavior in the resident-intruder test when compared to their wildtype littermates. Tph2\(^{+/-}\) mice showed an ambiguous profile with context-dependent, behavioral responses. In the EPM they showed similar avoidance of the open arm but decreased prosocial and increased rule breaking behavior in the resident-intruder test when compared to their wildtype littermates. Notably, MS effects on behavior were subtle and depended on the Tph2 genotype, in particular increasing the observed avoidance of EPM open arms in wildtype and Tph2\(^{+/-}\) mice when compared to their Tph2\(^{-/-}\) littermates. On the genomic level, the interaction of Tph2 genotype with MS differentially affected the expression of numerous genes, of which a subset showed an overlap with DNA methylation profiles at corresponding loci. Remarkably, changes in methylation nearby and expression of the gene encoding cholecystokinin, which were inversely correlated to each other, were associated with variations in anxiety-related phenotypes. In conclusion, next to various behavioral alterations, we identified gene expression and DNA methylation profiles to be associated with TPH2 inactivation and its interaction with MS, suggesting a gene-by-environment interaction-dependent, modulatory function of brain 5-HT availability.
Background: In principle, the elimination of malignancies by oncolytic virotherapy could proceed by different mechanisms - e.g. tumor cell specific oncolysis, destruction of the tumor vasculature or an anti-tumoral immunological response. In this study, we analyzed the contribution of these factors to elucidate the responsible mechanism for regression of human breast tumor xenografts upon colonization with an attenuated vaccinia virus (VACV). Methods: Breast tumor xenografts were analyzed 6 weeks post VACV infection (p.i.; regression phase) by immunohistochemistry and mouse-specific expression arrays. Viral-mediated oncolysis was determined by tumor growth analysis combined with microscopic studies of intratumoral virus distribution. The tumor vasculature was morphologically characterized by diameter and density measurements and vessel functionality was analyzed by lectin perfusion and extravasation studies. Immunological aspects of viral-mediated tumor regression were studied in either immune-deficient mouse strains (T-, B-, NK-cell-deficient) or upon cyclophosphamide-induced immunosuppression (MHCII+-cell depletion) in nude mice. Results: Late stage VACV-infected breast tumors showed extensive necrosis, which was highly specific to cancer cells. The tumor vasculature in infected tumor areas remained functional and the endothelial cells were not infected. However, viral colonization triggers hyperpermeability and dilatation of the tumor vessels, which resembled the activated endothelium in wounded tissue. Moreover, we demonstrated an increased expression of genes involved in leukocyte-endothelial cell interaction in VACV-infected tumors, which orchestrate perivascular inflammatory cell infiltration. The immunohistochemical analysis of infected tumors displayed intense infiltration of MHCII-positive cells and colocalization of tumor vessels with MHCII+/CD31+ vascular leukocytes. However, GI-101A tumor growth analysis upon VACV-infection in either immunosuppressed nude mice (MHCII+-cell depleted) or in immune-deficient mouse strains (T-, B-, NK-cell-deficient) revealed that neither MHCII-positive immune cells nor T-, B-, or NK cells contributed significantly to VACV-mediated tumor regression. In contrast, tumors of immunosuppressed mice showed enhanced viral spreading and tumor necrosis. Conclusions: Taken together, these results indicate that VACV-mediated oncolysis is the primary mechanism of tumor shrinkage in the late regression phase. Neither the destruction of the tumor vasculature nor the massive VACV-mediated intratumoral inflammation was a prerequisite for tumor regression. We propose that approaches to enhance viral replication and spread within the tumor microenvironment should improve therapeutical outcome.
Background
Oncolytic virotherapy of tumors is an up-coming, promising therapeutic modality of cancer therapy. Unfortunately, non-invasive techniques to evaluate the inflammatory host response to treatment are rare. Here, we evaluate \(^{19}\)F magnetic resonance imaging (MRI) which enables the non-invasive visualization of inflammatory processes in pathological conditions by the use of perfluorocarbon nanoemulsions (PFC) for monitoring of oncolytic virotherapy.
Methodology/Principal Findings
The Vaccinia virus strain GLV-1h68 was used as an oncolytic agent for the treatment of different tumor models. Systemic application of PFC emulsions followed by \(^1H\)/\(^{19}\)F MRI of mock-infected and GLV-1h68-infected tumor-bearing mice revealed a significant accumulation of the \(^{19}\)F signal in the tumor rim of virus-treated mice. Histological examination of tumors confirmed a similar spatial distribution of the \(^{19}\)F signal hot spots and \(CD68^+\)-macrophages. Thereby, the \(CD68^+\)-macrophages encapsulate the GFP-positive viral infection foci. In multiple tumor models, we specifically visualized early inflammatory cell recruitment in Vaccinia virus colonized tumors. Furthermore, we documented that the \(^{19}\)F signal correlated with the extent of viral spreading within tumors.
Conclusions/Significance
These results suggest \(^{19}\)F MRI as a non-invasive methodology to document the tumor-associated host immune response as well as the extent of intratumoral viral replication. Thus, \(^{19}\)F MRI represents a new platform to non-invasively investigate the role of the host immune response for therapeutic outcome of oncolytic virotherapy and individual patient response.
Background: Recent data suggest that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are responsible for relapses after apparently curative therapies have been undertaken. Hence, novel cancer therapies will be needed to test for both tumor regression and CSC targeting. The use of oncolytic vaccinia virus (VACV) represents an attractive anti-tumor approach and is currently under evaluation in clinical trials. The purpose of this study was to demonstrate whether VACV does kill CSCs that are resistant to irradiation and chemotherapy.
Methods: Cancer stem-like cells were identified and separated from the human breast cancer cell line GI-101A by virtue of increased aldehyde dehydrogenase 1 (ALDH1) activity as assessed by the ALDEFLUOR assay and cancer stem cell-like features such as chemo-resistance, irradiation-resistance and tumor-initiating were confirmed in cell culture and in animal models. VACV treatments were applied to both ALDEFLUOR-positive cells in cell culture and in xenograft tumors derived from these cells. Moreover, we identified and isolated CD44\(^+\)CD24\(^+\)ESA\(^+\) cells from GI-101A upon an epithelial-mesenchymal transition (EMT). These cells were similarly characterized both in cell culture and in animal models.
Results: We demonstrated for the first time that the oncolytic VACV GLV-1h68 strain replicated more efficiently in cells with higher ALDH1 activity that possessed stem cell-like features than in cells with lower ALDH1 activity. GLV-1h68 selectively colonized and eventually eradicated xenograft tumors originating from cells with higher ALDH1 activity. Furthermore, GLV-1h68 also showed preferential replication in CD44\(^+\)CD24\(^+\)ESA\(^+\) cells derived from GI-101A upon an EMT induction as well as in xenograft tumors originating from these cells that were more tumorigenic than CD44\(^+\)CD24\(^-\)ESA\(^+\) cells.
Conclusions: Taken together, our findings indicate that GLV-1h68 efficiently replicates and kills cancer stem-like cells. Thus, GLV-1h68 may become a promising agent for eradicating both primary and metastatic tumors, especially tumors harboring cancer stem-like cells that are resistant to chemo and/or radiotherapy and may be responsible for recurrence of tumors.
Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection.
Background: Searching the orthologs of a given protein or DNA sequence is one of the most important and most commonly used Bioinformatics methods in Biology. Programs like BLAST or the orthology search engine Inparanoid can be used to find orthologs when the similarity between two sequences is sufficiently high. They however fail when the level of conservation is low. The detection of remotely conserved proteins oftentimes involves sophisticated manual intervention that is difficult to automate.
Results: Here, we introduce morFeus, a search program to find remotely conserved orthologs. Based on relaxed sequence similarity searches, morFeus selects sequences based on the similarity of their alignments to the query, tests for orthology by iterative reciprocal BLAST searches and calculates a network score for the resulting network of orthologs that is a measure of orthology independent of the E-value. Detecting remotely conserved orthologs of a protein using morFeus thus requires no manual intervention. We demonstrate the performance of morFeus by comparing it to state-of-the-art orthology resources and methods. We provide an example of remotely conserved orthologs, which were experimentally shown to be functionally equivalent in the respective organisms and therefore meet the criteria of the orthology-function conjecture.
Conclusions: Based on our results, we conclude that morFeus is a powerful and specific search method for detecting remotely conserved orthologs.
Background
During development in human erythrocytes, Plasmodium falciparum parasites display a remarkable number of adhesive proteins on their plasma membrane. In the invasive merozoites, these include members of the PfMSP1 and PfAMA1/RON complexes, which facilitate contact between merozoites and red blood cells. In gametocytes, sexual precursor cells mediating parasite transmission to the mosquito vector, plasma membrane-associated proteins primarily belong to the PfCCp and 6-cys families with roles in fertilization. This study describes a newly identified WD40-repeat protein unique to Plasmodium species that associates with adhesion protein complexes of both merozoites and gametocytes.
Methods
The WD40-repeat protein-like protein PfWLP1 was identified via co-immunoprecipitation assays followed by mass spectrometry and characterized using biochemical and immunohistochemistry methods. Reverse genetics were employed for functional analysis.
Results
PfWLP1 is expressed both in schizonts and gametocytes. In mature schizonts, the protein localizes underneath the merozoite micronemes and interacts with PfAMA1, while in gametocytes PfWLP1 primarily accumulates underneath the plasma membrane and associates with PfCCp1 and Pfs230. Reverse genetics failed to disrupt the pfwlp1 gene, while haemagglutinin-tagging was feasible, suggesting a crucial function for PfWLP1 during blood stage replication.
Conclusions
This is the first report on a plasmodial WD40-repeat protein associating with cell adhesion proteins. Since WD40 domains are known to mediate protein–protein contact by serving as a rigid scaffold for protein interactions, the presented data suggest that PfWLP1 supports the stability of adhesion protein complexes of the plasmodial blood stages.
Our body is colonized by a vast array of bacteria the sum of which forms our microbiota. The gut alone harbors >1,000 bacterial species. An understanding of their individual or synergistic contributions to human health and disease demands means to interfere with their functions on the species level. Most of the currently available antibiotics are broad‐spectrum, thus too unspecific for a selective depletion of a single species of interest from the microbiota. Programmable RNA antibiotics in the form of short antisense oligonucleotides (ASOs) promise to achieve precision manipulation of bacterial communities. These ASOs are coupled to small peptides that carry them inside the bacteria to silence mRNAs of essential genes, for example, to target antibiotic‐resistant pathogens as an alternative to standard antibiotics. There is already proof‐of‐principle with diverse bacteria, but many open questions remain with respect to true species specificity, potential off‐targeting, choice of peptides for delivery, bacterial resistance mechanisms and the host response. While there is unlikely a one‐fits‐all solution for all microbiome species, I will discuss how recent progress in bacterial RNA biology may help to accelerate the development of programmable RNA antibiotics for microbiome editing and other applications.