A5047315437- Antimicrobial Resistance in Staphylococcus
- Bacterial Genetics and Biotechnology
- Bacterial biofilms and quorum sensing
- Biochemical and Structural Characterization
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- ATP Synthase and ATPases Research
- Heat shock proteins research
- Ubiquitin and proteasome pathways
- T-cell and B-cell Immunology
- Fungal and yeast genetics research
- Immunotherapy and Immune Responses
- Genomics and Phylogenetic Studies
- Caveolin-1 and cellular processes
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Microbial Natural Products and Biosynthesis
- interferon and immune responses
- Antimicrobial Peptides and Activities
- Microbial infections and disease research
- Cancer Research and Treatments
- Amino Acid Enzymes and Metabolism
- Biopolymer Synthesis and Applications
University of Würzburg
2014-2023
University of Tübingen
2012-2019
Institute of Medical Microbiology and Hygiene
2013
Universitätsklinikum Tübingen
2011
National Institutes of Health Clinical Center
2006
Summary RNase Y of Bacillus subtilis is a key member the degradosome and important for bulk mRNA turnover. In contrast to B. , homologue ( rny/cvfA ) Staphylococcus aureus not essential growth . Here we found that plays major role in virulence gene regulation. Accordingly, rny deletion mutants demonstrated impaired murine bacteraemia model. processing stabilization immature transcript global regulator system SaePQRS. Moreover, involved activation expression at promoter level. This control...
A set of vectors for improved tetracycline-dependent gene regulation in Staphylococcus aureus is presented. Plasmid pRAB11 was generated from pRMC2 by adding a second tet operator within the TetR-regulated promoter P xyl/tet . Pronounced repression observed absence anhydrotetracycline (ATc) combined with high induction presence drug, as demonstrated bearing staphylococcal nuclease nuc1 , lacZ or gfp Also, plasmid pCG261, tetR –P regulatory architecture permitted tight and stepwise increase...
Coagulase-negative staphylococci (CoNS) are common opportunistic pathogens, but also ubiquitous human and animal commensals. Infection-associated CoNS from healthcare environments typically characterized by pronounced antimicrobial resistance (AMR) including both methicillin- multidrug-resistant isolates. Less is known about AMR patterns of colonizing the general population. Here we report on in commensal recovered 117 non-hospitalized volunteers a region Germany with high livestock density....
Scaffold proteins are ubiquitous chaperones that promote efficient interactions between partners of multi-enzymatic protein complexes; although they well studied in eukaryotes, their role prokaryotic systems is poorly understood. Bacterial membranes have functional membrane microdomains (FMM), a structure homologous to eukaryotic lipid rafts. Similar counterparts, bacterial FMM harbor scaffold termed flotillin thought spatially confined the FMM. Here we used biochemical approaches define...
RsaE is a conserved small regulatory RNA (sRNA) which was previously reported to represent riboregulator of central carbon flow and other metabolic pathways in Staphylococcus aureus Bacillus subtilis. Here we show that contributes extracellular (e)DNA release biofilm-matrix switching towards polysaccharide intercellular adhesin (PIA) production hypervariable epidermidis isolate. Transcriptome analysis through differential sequencing (dRNA-seq) combination with confocal laser scanning...
Polysaccharide intercellular adhesin (PIA)-associated biofilm formation is mediated by the (ica) locus and represents a major pathomechanism of Staphylococcus epidermidis. Here, we report on novel long non-coding (nc)RNA, named IcaZ, which approximately 400 nucleotides in size. icaZ located downstream ica repressor gene icaR partially overlaps with 3' UTR. exclusively exists ica-positive S. epidermidis, but not aureus or other staphylococci. Inactivation completely abolishes PIA production....
Staphylococcus aureus is one of the most frequent causes nosocomial and community-acquired infections, with drug-resistant strains being responsible for tens thousands deaths per year. S. sortase A inhibitors are designed to interfere virulence determinants. We have identified disulfanylbenzamides as a new class potent against that act by covalent modification active-site cysteine. broad series derivatives were synthesized derive structure-activity relationships (SAR). In vitro in silico...
Capsular polysaccharide (CP) biosynthesis in Staphylococcus aureus is tightly controlled resulting a heterogeneous phenotype within population and CP being mainly detectable nongrowing cells. Expression of the corresponding gene cluster driven by one promoter element (Pcap ). Here, we demonstrate that Pcap contains main SigB-dependent promoter. The SigB consensus motif overlaps with previously described inverted repeat (IR) crucial for cap expression. essentiality IR derived from this region...
Abstract Background It has been shown previously that aminocoumarin antibiotics such as novobiocin lead to immediate downregulation of recA expression and thereby inhibit the SOS response, mutation frequency recombination capacity in Staphylococcus aureus . Aminocoumarins function by inhibiting ATPase activity DNA gyrase subunit B with a severe impact on supercoiling. Results Here, we have analysed global relaxing agent gene S. Using novobiocin-resistant mutant, it became evident change is...
In gram-positive bacteria, RNase J1, J2 and Y are thought to be major contributors mRNA degradation maturation. Staphylococcus aureus, activity is restricted regulating the decay of only certain transcripts. Here saePQRS operon was used as a model analyze specificity in living cells. A cleavage site located an intergenic region between saeP saeQ. This resulted rapid upstream fragment stabilization downstream fragment. Thereby, expression ratio different components shifted towards saeRS,...
In line with the key role of methionine in protein biosynthesis initiation and many cellular processes most microorganisms have evolved mechanisms to synthesize de novo. Here we demonstrate that, bacterial pathogen Staphylococcus aureus, a rare combination stringent response-controlled CodY activity, T-box riboswitch mRNA decay regulate synthesis stability metICFE-mdh mRNA. contrast other Bacillales which employ S-box riboswitches control biosynthesis, S. aureus is preceded by...
Abstract Functionality of the accessory gene regulator ( agr ) quorum sensing system is an important factor promoting either acute or chronic infections by notorious opportunistic human and veterinary pathogen Staphylococcus aureus . Spontaneous alterations are known to frequently occur in healthcare-associated S. lineages. However, data on integrity function sparse regarding other major clonal Here we report functionality activity level mec C-carrying methicillin resistant (MRSA) various...
In Staphylococcus aureus, de novo methionine biosynthesis is regulated by a unique hierarchical pathway involving stringent-response controlled CodY repression in combination with T-box riboswitch and RNA decay. The residing the 5' untranslated region (met leader RNA) of S. aureus metICFE-mdh operon controls downstream gene transcription upon interaction uncharged methionyl-tRNA. met (m)RNAs undergo RNase-mediated degradation process whose molecular details are poorly understood. Here we...
The Staphylococcus aureus regulatory saePQRS system controls the expression of numerous virulence factors, including extracellular adherence protein (Eap), which amongst others facilitates invasion host cells. operon codes for 4 proteins: histidine kinase SaeS, response regulator SaeR, lipoprotein SaeP and transmembrane SaeQ. S. strain Newman has a single amino acid substitution in domain SaeS (L18P) results constitutive activity. SDS was shown to be one signals interfering with activity...
The ATPase p97 (also known as VCP, Cdc48) has crucial functions in a variety of important cellular processes such protein quality control, organellar homeostasis, and DNA damage repair, its de-regulation is linked to neuromuscular diseases cancer. tightly controlled by numerous regulatory cofactors, but the full range function p97–cofactor network unknown. Here, we identify hitherto uncharacterized FAM104 proteins conserved family interactors. two human members V CP nuclear c ofactor f amily...
Non-aureus staphylococci (NAS) are ubiquitous bacteria in livestock-associated environments where they may act as reservoirs of antimicrobial resistance (AMR) genes for pathogens such Staphylococcus aureus. Here, we tested whether housing conditions pig farms could influence the overall AMR-NAS burden. Two hundred and forty porcine commensal environmental NAS isolates from three different farm types (conventional, alternative, organic) were phenotypic susceptibility subjected to whole genome...
Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) of clonal complex CC398 typically carry various antimicrobial resistance genes, many them located on plasmids. In the bovine LA-MRSA isolate Rd11, we previously identified plasmid pAFS11 in which genes are co-localized with a novel ica-like gene cluster, harboring required for polysaccharide intercellular adhesin (PIA)-mediated biofilm formation. The ica were acquired addition to pre-existing locus S. Rd11 chromosomal...
Abstract In Staphylococcus aureus , the capsular polysaccharide (CP) protects against phagocytosis, but also hinders adherence to endothelial cells and matrix proteins. Its biosynthesis is tightly controlled resulting in a heterogeneous phenotype within population CP being mainly detectable non-growing cells. Capsular genes are encoded by conserved capA-P operon whose expression driven an upstream promoter element (P cap ) front of capA . The organization P poorly understood, as interplay...
Abstract The ATPase p97 (also known as VCP, Cdc48) has crucial functions in a variety of important cellular processes such protein quality control, organellar homeostasis and DNA damage repair, its de-regulation is linked to neuro-muscular diseases cancer. tightly controlled by numerous regulatory cofactors, but the full range function p97–cofactor network unknown. Here, we identify hitherto uncharacterized FAM104 proteins conserved family interactors. bind directly via novel, alpha-helical...