- Antimicrobial Resistance in Staphylococcus
- Bacterial biofilms and quorum sensing
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Biochemical and Structural Characterization
- Antimicrobial Peptides and Activities
- RNA and protein synthesis mechanisms
- Antibiotic Resistance in Bacteria
- Streptococcal Infections and Treatments
- Bacterial Identification and Susceptibility Testing
- Microbial infections and disease research
- Immune Response and Inflammation
- Antifungal resistance and susceptibility
- Plant Pathogenic Bacteria Studies
- Genomics and Phylogenetic Studies
- Cystic Fibrosis Research Advances
- Bacillus and Francisella bacterial research
- Erythrocyte Function and Pathophysiology
- Vibrio bacteria research studies
- Microbial Metabolism and Applications
- Mycobacterium research and diagnosis
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Dermatology and Skin Diseases
- Nosocomial Infections in ICU
University of Tübingen
2016-2025
German Center for Infection Research
2014-2024
Czech Academy of Sciences, Institute of Microbiology
2010-2024
Institute of Medical Microbiology and Hygiene
2008-2021
Universitätsklinikum Tübingen
2005-2018
Leibniz-Institut für Wissensmedien
2012
Dartmouth College
2007
TH Bingen University of Applied Sciences
2005
Institut für Hygiene und Umwelt
2000-2004
Rockefeller University
1995-2000
Abstract Bacterial persister cells are phenotypic variants that exhibit a transient non-growing state and antibiotic tolerance. Here, we provide in vitro evidence of Staphylococcus aureus persisters within infected host cells. We show the bacteria surviving treatment persisters, displaying biphasic killing reaching uniformly non-responsive, non-dividing when followed at single-cell level. This phenotype is stable but reversible upon removal. Intracellular S. remain metabolically active...
Temperate bacteriophages play an important role in the pathogenicity of Staphylococcus aureus, for instance, by mediating horizontal gene transfer virulence factors. Here we established a classification scheme staphylococcal prophages major Siphoviridae family based on integrase polymorphism. Seventy-one published genome sequences phages were clustered into distinct groups which related to chromosomal integration site and encoded content. Analysis three marker modules (lysogeny, tail, lysis)...
The stringent response is initiated by rapid (p)ppGpp synthesis, which leads to a profound reprogramming of gene expression in most bacteria. phenotype seems be species specific and may mediated fundamentally different molecular mechanisms. In Staphylococcus aureus, synthesis upon amino acid deprivation achieved through the synthase domain bifunctional enzyme RSH (RelA/SpoT homolog). several firmicutes, direct link between CodY regulon was proposed. Wild-type strain HG001, rshSyn, codY...
The repressor CodY is reported to inhibit metabolic genes mainly involved in nitrogen metabolism. We analyzed codY mutants from three unrelated Staphylococcus aureus strains (Newman, UAMS-1, and RN1HG). grew more slowly than their parent a chemically defined medium. However, only were able grow medium lacking threonine. An excess of isoleucine resulted growth inhibition the wild type but not mutants, indicating that plays role CodY-dependent repression. Prototypic CodY-repressed including...
ABSTRACT In Staphylococcus aureus strains of human origin, phages which integrate into the chromosomal gene coding for β-hemolysin ( hlb ) are widely distributed. Most them encode accessory virulence determinants such as staphylokinase sak or enterotoxins. Here, we analyzed effects ciprofloxacin and trimethoprim on phage induction expression phage-encoded factors by using isolates from patients with cystic fibrosis -converting was demonstrated in vivo (C. Goerke, S. Matias y Papenberg,...
ABSTRACT Bacteria possess a repertoire of distinct regulatory systems promoting survival in disparate environments. Under vitro conditions it was demonstrated for the human pathogen Staphylococcus aureus that expression most virulence factors is coordinated by global regulator agr . To monitor bacterial gene regulation host, we developed method direct transcript analysis from clinical specimens. Quantification specific transcripts performed competitive reverse transcription-PCR, and results...
ABSTRACT Carbon catabolite protein A (CcpA) is known to function as a major regulator of gene expression in different gram-positive organisms. Deletion the ccpA homologue ( saCOL1786 ) Staphylococcus aureus was found affect growth, glucose metabolization, and transcription selected virulence determinants. In liquid culture, deletion CcpA decreased growth rate yield; however, effect only transient during exponential-growth phase long present medium. Depletion production lactate delayed, while...
The two-component system SaeRS consisting of the histidin kinase SaeS and response regulator SaeR is known to act on virulence gene expression in Staphylococcus aureus. In order get a more comprehensive picture SaeR-regulated genes, we studied contribution global by using both proteomic transcriptomic approach. Altogether, loss resulted decreased amount at least 17 extracellular proteins two cell surface-associated proteins, among them several important factors such as HlgA, HlgB, HlgC,...
The stringent response is a conserved global regulatory mechanism that related to the synthesis of (p)ppGpp nucleotides. Gram-positive bacteria, such as Staphylococcus aureus, possess three synthases: bifunctional RSH (RelA/SpoT homolog) protein, which consists synthase and hydrolase domain, two truncated synthases, designated RelP RelQ. Here, we characterized these small synthases. Biochemical analyses purified proteins in vivo studies revealed stronger synthetic activity for than However,...
ABSTRACT The two-component system SaeRS of Staphylococcus aureus is closely involved in the regulation major virulence factors. However, little known about signals leading to saeRS activation. A total four overlapping transcripts (T1 T4) from three different transcription starting points are expressed sae operon. We used a β-galactosidase reporter assay characterize putative promoter regions within upstream region. main transcript T2 probably generated by endoribonucleolytic processing T1...
ABSTRACT Biofilm formation in Staphylococcus aureus under vitro growth conditions is generally promoted by high concentrations of sugar and/or salts. The addition glucose to routinely used complex media triggered biofilm S. strain SA113. Deletion ccpA , coding for the catabolite control protein A (CcpA), which regulates gene expression response carbon source, abolished capacity SA113 form a static and flow conditions, while still allowing primary attachment polystyrene surfaces. This...
Staphylococcus aureus is a Gram-positive human pathogen that readily internalized by professional phagocytes such as macrophages and neutrophils but also non-professional epithelial or endothelial cells. Intracellular bacteria have been proposed to play role in evasion of the innate immune system may lead dissemination within migrating phagocytes. Further, S. efficiently lyses host cells with battery cytolytic toxins. Recently, phenol-soluble modulins (PSM) identified comprise genus-specific...
In most bacteria, nutrient limitations provoke the stringent control through rapid synthesis of alarmones pppGpp and ppGpp. Little is known about in human pathogen Staphylococcus aureus, partly due to essentiality major (p)ppGpp synthase/hydrolase enzyme RSH (RelA/SpoT homolog). Here, we show that mutants defective only synthase domain (rsh(syn)) are not impaired growth under nutrient-rich conditions. However, these were more sensitive toward mupirocin survival when essential amino acids...
ABSTRACT The saePQRS system of Staphylococcus aureus controls the expression major virulence factors and encodes a histidine kinase (SaeS), response regulator (SaeR), membrane protein (SaeQ), lipoprotein (SaeP). widely used strain Newman is characterized by single amino acid change in sensory domain SaeS (Pro18 [SaeS P ], compared with Leu18 other strains L ]). determines activation class I sae target genes ( coa , fnbA eap sib efb fib ), which are highly expressed Newman. In contrast, II...
The human pathogen Staphylococcus aureus successfully colonizes its primary reservoir, the nasal cavity, most likely by regulatory adaptation to nose environment. Cotton rats represent an excellent model for study of bacterial gene expression in initial phases colonization. To gain insight into profile necessary establishment colonization, we performed direct transcript analysis quantitative real-time reverse-transcription polymerase chain reaction on cotton rat noses removed from euthanized...
Sepsis caused by Gram-positive bacterial pathogens is a major fatal disease but its molecular basis remains elusive. Toll-like receptor 2 (TLR2) has been implicated in the orchestration of inflammation and sepsis role appears to vary for different pathogen species clones. Accordingly, Staphylococcus aureus clinical isolates differ substantially their capacity activate TLR2. Here we show that strong TLR2 stimulation depends on high-level production phenol-soluble modulin (PSM) peptides...
ObjectivesCo-trimoxazole (trimethoprim/sulfamethoxazole) is clinically valuable in treating skin and soft tissue infections (SSTIs) caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA). The genetic basis of emerging trimethoprim/sulfamethoxazole resistance S. from Africa unknown. Such knowledge essential to anticipate its further spread. We investigated the molecular epidemiology trimethoprim collected imported Africa.